RESUMEN
Benzodiazepines are commonly used drugs to treat anxiety in crime witnesses. These increase GABA inhibitory effects, which impairs aversive memory encoding and consolidation. Eyewitness memory is essential in justice. However, memory is malleable leading to false memories that could cause a selection of an innocent in a lineup. Here, we studied whether a low dose of Clonazepam impairs memory encoding as well as consolidation of faces and narrative of the event. We performed two experiments using a double-blind and between subject design (N = 216). Day 1: subjects watched a crime video and received Clonazepam 0.25 mg (CLZ group) or placebo (PLC group) before (Exp. 1) or after the video (Exp. 2) to assess the effect on encoding and consolidation. One week later, the memory was assessed using a present and absent target lineup and asking for a free recall. Regarding encoding, we found that in the CLZ group memory was impaired in the free recall task, while no differences were found for recognition memory. Regarding consolidation, we did not observe memory measures that were affected by this dose of benzodiazepines. The results suggest that while some aspects of eyewitness memory could be modulated even with low doses of benzodiazepine, others could not be affected. More studies should be performed with higher doses of CLZ similar to those administered in real life. These results are relevant in the judicial field to assess the reliability of the eyewitness elections under the effects of this drug.
Asunto(s)
Clonazepam , Reconocimiento Facial , Recuerdo Mental , Humanos , Reconocimiento Facial/efectos de los fármacos , Reconocimiento Facial/fisiología , Masculino , Método Doble Ciego , Clonazepam/farmacología , Adulto Joven , Femenino , Adulto , Recuerdo Mental/efectos de los fármacos , Consolidación de la Memoria/efectos de los fármacos , Reconocimiento en Psicología/efectos de los fármacos , AdolescenteRESUMEN
The destabilization/reconsolidation process can be triggered by memory recall, allowing consolidated memories to be modified. We have previously reported that stress prior to fear conditioning induces memories that exhibit resistance to the engagement of some molecular events associated with the destabilization/reconsolidation process. Here, we evaluated whether stress could affect the expression of Lys-48 polyubiquitinated proteins within the basolateral amygdala complex, a phenomenon crucially linked to memory destabilization. As expected, a post-recall increase of Lys-48 polyubiquitinated proteins in control animals was observed; however, this phenomenon was prevented by stress exposure before fear conditioning. On the other hand, pre-recall administration of D-cycloserine -a positive modulator of NMDA sites capable of reverting memory resistance to pharmacological interference-, facilitated the increase of Lys-48 polyubiquitinated proteins in stressed animals. In conclusion, the protein polyubiquitination-dependent destabilization is impaired after the recall of stress-induced resistant memories, with D-cycloserine restoring such molecular event. Hence, the present report contributes to further characterize the neurobiological events associated with stress-induced memory resistance as well as to corroborate the connection between glutamatergic signaling, protein degradation and memory destabilization in stress-induced resistant memories.
Asunto(s)
Complejo Nuclear Basolateral/metabolismo , Condicionamiento Clásico/fisiología , Miedo , Consolidación de la Memoria/fisiología , Recuerdo Mental/fisiología , Estrés Psicológico/metabolismo , Animales , Complejo Nuclear Basolateral/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Cicloserina/farmacología , Masculino , Memoria/efectos de los fármacos , Memoria/fisiología , Consolidación de la Memoria/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Poliubiquitina/metabolismo , Ratas , Ubiquitinación/efectos de los fármacosRESUMEN
Fear-motivated avoidance extinction memory is prone to hippocampal brain-derived neurotrophic factor (BDNF)-dependent reconsolidation upon recall. Here, we show that extinction memory recall activates mammalian target of rapamycin (mTOR) in dorsal CA1, and that post-recall inhibition of this kinase hinders avoidance extinction memory persistence and recovers the learned aversive response. Importantly, coadministration of recombinant BDNF impedes the behavioral effect of hippocampal mTOR inhibition. Our results demonstrate that mTOR signaling is necessary for fear-motivated avoidance extinction memory reconsolidation and suggests that BDNF acts downstream mTOR in a protein synthesis-independent manner to maintain the reactivated extinction memory trace.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/farmacología , Región CA1 Hipocampal/metabolismo , Extinción Psicológica/fisiología , Consolidación de la Memoria/fisiología , Recuerdo Mental/fisiología , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Región CA1 Hipocampal/efectos de los fármacos , Extinción Psicológica/efectos de los fármacos , Miedo/efectos de los fármacos , Miedo/fisiología , Consolidación de la Memoria/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Proteínas Recombinantes , Transducción de Señal/efectos de los fármacosRESUMEN
The sense of taste provides information regarding the nutrient content, safety or potential toxicity of an edible. This is accomplished via a combination of innate and learned taste preferences. In conditioned taste aversion (CTA), rats learn to avoid ingesting a taste that has previously been paired with gastric malaise. Recent evidence points to a role of cholinergic muscarinic signaling in the amygdala for the learning and storage of emotional memories. The present study tested the participation of muscarinic receptors in the amygdala during the formation of CTA by infusing the non-specific antagonist scopolamine into the basolateral or central subnuclei before or after conditioning, as well as before retrieval. Our data show that regardless of the site of infusion, pre-conditioning administration of scopolamine impaired CTA acquisition whereas post-conditioning infusion did not affect its storage. Also, infusions into the basolateral but not in the central amygdala before retrieval test partially reduced the expression of CTA. Our results indicate that muscarinic receptors activity is required for acquisition but not consolidation of CTA. In addition, our data add to recent evidence pointing to a role of cholinergic signaling in peri-hippocampal structures in the process of memory retrieval.
Asunto(s)
Amígdala del Cerebelo/fisiología , Reacción de Prevención/fisiología , Receptores Muscarínicos/fisiología , Transducción de Señal/fisiología , Gusto/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Reacción de Prevención/efectos de los fármacos , Emociones , Masculino , Consolidación de la Memoria/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Microinyecciones , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/farmacología , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/fisiología , Ratas , Ratas Wistar , Receptores Muscarínicos/efectos de los fármacos , Escopolamina/administración & dosificación , Escopolamina/farmacología , Transducción de Señal/efectos de los fármacos , Gusto/efectos de los fármacosRESUMEN
Recently, it was reported that mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity during memory retrieval is required for normal expression of aversive and non-aversive long-term memories. Here we used inhibitory-avoidance task to evaluate the potential mechanisms by which mTORC1 signaling pathway participates in memory retrieval. First, we studied the role of GluA-subunit trafficking during memory recall and its relationship with mTORC1 pathway. We found that pretest intrahippocampal infusion of GluR23É£, a peptide that selectively blocks GluA2-containing AMPA receptor (AMPAR) endocytosis, prevented the amnesia induced by the inhibition of mTORC1 during retrieval. Additionally, we found that GluA1 levels decreased and GluA2 levels increased at the hippocampal postsynaptic density subcellular fraction of rapamycin-infused animals during memory retrieval. GluA2 levels remained intact while GluA1 decreased at the synaptic plasma membrane fraction. Then, we evaluated the requirement of AMPAR subunit expression during memory retrieval. Intrahippocampal infusion of GluA1 or GluA2 antisense oligonucleotides (ASO) 3 h before testing impaired memory retention. The memory impairment induced by GluA2 ASO before retrieval was reverted by GluA23É£ infusion 1 h before testing. However, AMPAR endocytosis blockade was not sufficient to compensate GluA1 synthesis inhibition. Our work indicates that de novo GluA1 and GluA2 AMPAR subunit expression is required for memory retrieval with potential different roles for each subunit and suggests that mTORC1 might regulate AMPAR trafficking during retrieval. Our present results highlight the role of mTORC1 as a key determinant of memory retrieval that impacts the recruitment of different AMPAR subunits.
Asunto(s)
Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Memoria a Largo Plazo , Recuerdo Mental , Receptores AMPA/metabolismo , Transducción de Señal , Animales , Reacción de Prevención/efectos de los fármacos , Endocitosis/efectos de los fármacos , Masculino , Trastornos de la Memoria/fisiopatología , Memoria a Largo Plazo/efectos de los fármacos , Memoria a Largo Plazo/fisiología , Recuerdo Mental/efectos de los fármacos , Recuerdo Mental/fisiología , Modelos Biológicos , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacologíaRESUMEN
Memory is one of the most important capabilities of our mind since it determines our individuality. Memory formation involves different stages: acquisition, consolidation and retrieval. There are many studies about early stages, however little is known about memory retrieval. Retrieval is the use of learned information and represents a big problem in patients with memory deficits where the main issue is that they can learn but cannot remember. Previous findings have demonstrated that 5-hydroxytryptamine (5-HT) is a neurotransmitter involved in memory process. Hence, here we are exploring the role of 5-HT in memory retrieval by using its metabolic precursor l-tryptophan and several ligands at 5-HT1A and 5-HT7 receptors. Experimental protocol consisted of evaluating conditioned responses (%CR) after one week of interruption following autoshaping sessions for memory formation; a decrease of %CR was interpreted as memory decay. Systemic administration of: (1) l-tryptophan (50 and 100 mg/kg), (2) 5-HT1A receptor agonist 8-OH-DPAT (0.031 and 0.062 mg/kg), (3) the selective antagonist 5-HT1A receptor WAY 100635 (0.3 and 0.6 mg/kg), (4) the 5-HT7 receptor agonist, LP 211, in a dose-dependent manner (1, 2.5, 5.0 and 10.0 mg/kg) enhanced memory retrieval. Further, the 5-HT7 receptor antagonist, SB 269970 (10.0 mg/kg), had no effect. Finally, SB 269970 (10.0 mg/kg) significantly blocked memory retrieval enhancement produced by 10.0 mg/kg LP 211, but not that induced by 2.5 mg/kg LP 211.These results, taken together, suggest that activation of 5-HT1A and 5-HT7 receptors enhanced memory retrieval and these receptors may be therapeutic targets to improve long-term memory retrieval.
Asunto(s)
Condicionamiento Operante/efectos de los fármacos , Memoria a Largo Plazo/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Receptor de Serotonina 5-HT1A/efectos de los fármacos , Receptores de Serotonina/efectos de los fármacos , Refuerzo en Psicología , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología , Triptófano/farmacología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Conducta Animal/efectos de los fármacos , Masculino , Piperazinas/farmacología , Piridinas/farmacología , Ratas Wistar , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Antagonistas de la Serotonina/administración & dosificación , Agonistas de Receptores de Serotonina/administración & dosificación , Triptófano/administración & dosificaciónRESUMEN
Reconsolidation is a time-limited process under which reactivated memory content can be modified. Works focused on studying reconsolidation mainly restrict intervention to the moments immediately after reactivation and to recently acquired memories. However, the brain areas activated during memory retrieval depend on when it was acquired, and it is relatively unknown how different brain sites contribute to reconsolidation and persistence of reactivated recent and remote fear memories. Here, we sought to investigate the participation of prelimbic (PL) and anterior cingulate cortices (ACC) in recent (1 d old) and remote (21 d old) fear memory reconsolidation and persistence. Male Wistar rats were submitted to the contextual fear conditioning protocol. Tamoxifen (TMX), an estrogen receptor modulator known to inhibit protein kinase C activity was used to interfere with these processes. When infused into the PL cortex, but not into the ACC, TMX administration immediately or 6 h after recent fear memory reactivation impaired memory reconsolidation and persistence, respectively. TMX administered immediately after remote memory reactivation impaired memory reconsolidation when infused into the PL cortex and ACC. However, remote memory persistence was only affected when TMX was infused 6 h after memory reactivation into the ACC and no effect was observed when TMX was infused 6 h after memory reactivation into PL cortex. Together, the findings provide further evidence on the participation of PL cortex and ACC in reconsolidation of recent and remote fear memories and suggest that the persistence of a reactivated fear memory becomes independent on the PL cortex with memory age and dependent on the ACC.
Asunto(s)
Miedo/fisiología , Giro del Cíngulo/fisiología , Consolidación de la Memoria/fisiología , Memoria a Largo Plazo/fisiología , Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Giro del Cíngulo/efectos de los fármacos , Masculino , Consolidación de la Memoria/efectos de los fármacos , Memoria a Largo Plazo/efectos de los fármacos , Memoria a Corto Plazo/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Ratas , Ratas Wistar , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Tamoxifeno/farmacología , Factores de TiempoRESUMEN
Differences in cytoarchitectural organization and connectivity distinguishes granular (or area 29, A29) and dysgranular (or area 30, A30) subdivisions of the retrosplenial cortex (RSC). Although increasing evidence supports the participation of RSC in contextual fear learning and memory, the contribution of each RSC subdivision remains unknown. Here we used orchiectomized rats and intraperitoneal (i.p.) injections of saline (control) or 5 mg/kg MK801, to trigger selective degeneration of pyramidal neurons in layers IV-Va of A29 (A29MK801 neurons). These treatments were applied 3 days before or two days after contextual fear conditioning, and contextual fear memory was evaluated by scoring freezing in the conditioned context five days after training. Afterwards, brains were fixed and c-Fos and Egr-1 expression were assessed as surrogates of neuronal activity elicited by the recall in A29, A30 and in limbic areas. We found that eliminating A29MK801 neurons after training reduces conditioned freezing to 43.1 ± 9.9% respect to control rats. This was associated with a significant reduction of c-Fos and Egr-1 expression in A30, but not in other limbic areas. On the other hand, eliminating A29MK801 neurons before training caused a mild but significant reduction of conditioned freezing to 79.7 ± 6.8%, which was associated to enhanced expression of c-Fos in A29, A30 and CA1 field of hippocampus, while Egr-1 expression in caudomedial (CEnt) entorhinal cortex was not depressed as in control animals. These observations show that severeness of amnesia differs according to whether A29MK801 neurons were eliminated before or after conditioning, likely because loss of A29MK801 neurons after conditioning disrupt memory engram while their elimination before training allow recruitment of other neurons in A29 for partial compensation of contextual fear learning and memory. These observations add further support for the critical role of A29MK801 neurons in contextual fear learning and memory by connecting limbic structures with A30.
Asunto(s)
Amnesia/fisiopatología , Miedo/fisiología , Hipocampo/fisiopatología , Recuerdo Mental/fisiología , Neuronas/fisiología , Amnesia/metabolismo , Animales , Maleato de Dizocilpina/toxicidad , Miedo/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Recuerdo Mental/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , RatasRESUMEN
In the last decade it became clear that a previously consolidated memory can be modified during the plastic state induced by retrieval. This updating process opens the possibility to adapt undesired memory. Here we investigated whether fear memory could be updated to less-aversive/positive level by inserting hedonic information during retrieval. Considering that methylphenidate has strong rewarding propriety, we injected 3 or 10 mg/kg pre or post-reactivation in rats previously trained in contextual fear conditioning. We found that memory reactivation under effect of methylphenidate attenuates fear memory within-session and in subsequent tests in a drug-free condition, without presenting spontaneous recovery. Interestingly, methylphenidate impaired memory extinction when injected before, but not after a long reactivation session. We also showed that methylphenidate induces place preference and increases motor activity. Thus, this study provides new insights in the memory updating process and suggests that a previously consolidated fear memory can be attenuated by inserting appetitive information during retrieval.
Asunto(s)
Estimulantes del Sistema Nervioso Central/farmacología , Miedo/efectos de los fármacos , Miedo/psicología , Memoria/efectos de los fármacos , Metilfenidato/farmacología , Recompensa , Animales , Condicionamiento Operante/efectos de los fármacos , Condicionamiento Psicológico/efectos de los fármacos , Extinción Psicológica/efectos de los fármacos , Masculino , Consolidación de la Memoria , Recuerdo Mental/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Placer , Ratas , Ratas WistarRESUMEN
BACKGROUND: There is concern about the cognitive consequences of marijuana consumption. AIM: To assess the influence of current and past marijuana use and frequency on verbal learning and memory in a sample of adults aged 21 years old. MATERIAL AND METHODS: Marijuana use was assessed using a clinician administered interview in 654 participants (56% females), who reported frequency of use, age of first use and whether its use led to problems in their lives. The CogState International Shopping List was administered to assess learning and memory. RESULTS: Seventy percent reported ever using marijuana, 46% consuming during the past year and 27% during the past 30 days. The latter scored significantly lower on delayed recall. Current and frequent use were significantly associated with lower accuracy in verbal learning and memory. CONCLUSIONS: In this cohort of adults aged 21 years old, marijuana use was prevalent and related to worse verbal memory.
Asunto(s)
Cannabinoides/farmacología , Uso de la Marihuana/epidemiología , Memoria/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Aprendizaje Verbal/efectos de los fármacos , Chile/epidemiología , Trastornos del Conocimiento/complicaciones , Estudios Transversales , Femenino , Humanos , Masculino , Abuso de Marihuana/epidemiología , Abuso de Marihuana/etiología , Uso de la Marihuana/efectos adversos , Pruebas Neuropsicológicas , Factores de Tiempo , Adulto JovenRESUMEN
Fear memory reactivation does not always lead to memory destabilization-reconsolidation. For instance, fear memories formed following withdrawal from chronic ethanol consumption or a stressful event are less likely to become destabilized after reactivation, with the effect of recall of these memories on the affective state still requiring elucidation. Here, we investigated the negative emotional-like responses following fear memory reactivation in ethanol-withdrawn (ETOH) rats by focusing on the possible role played by destabilization. Our findings indicated that ETOH rats displayed an increased freezing in a novel context and an anxiogenic-like response in the elevated plus maze (EPM) following memory reactivation, whereas the behavior of CON animals was not affected. The destabilization blockade by pre-reactivation nimodipine (16â¯mg/kg, s.c) administration promoted in CON animals a similar behavior in the EPM and in a novel environment as that exhibited by ETOH rats after the reminder. Moreover, facilitating destabilization by pre-reactivation d-cycloserine (5â¯mg/kg, i.p) administration prevented the emotional-like disturbances observed in ETOH rats. Finally, using restraint stress, which is also an inductor of a fear memory resistant to destabilization, an increased fear response in an unconditioned environment and an anxiogenic-like state was also found after the presentation of the fear reminder in stressed rats. Our results suggest that, in the context of resistant fear memories, the occurrence of destabilization influences how animals respond to subsequent environmental challenges following reactivation.
Asunto(s)
Emociones , Miedo/psicología , Memoria , Recuerdo Mental , Animales , Condicionamiento Clásico , Cicloserina/farmacología , Emociones/efectos de los fármacos , Etanol/efectos adversos , Miedo/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Nimodipina/farmacología , Ratas , Ratas Wistar , Estrés Psicológico/psicología , Síndrome de Abstinencia a Sustancias/psicologíaRESUMEN
ABSTRACT Background: There is concern about the cognitive consequences of marijuana consumption. Aim: To assess the influence of current and past marijuana use and frequency on verbal learning and memory in a sample of adults aged 21 years old. Material and Methods: Marijuana use was assessed using a clinician administered interview in 654 participants (56% females), who reported frequency of use, age of first use and whether its use led to problems in their lives. The CogState International Shopping List was administered to assess learning and memory. Results: Seventy percent reported ever using marijuana, 46% consuming during the past year and 27% during the past 30 days. The latter scored significantly lower on delayed recall. Current and frequent use were significantly associated with lower accuracy in verbal learning and memory. Conclusions: In this cohort of adults aged 21 years old, marijuana use was prevalent and related to worse verbal memory.
Antecedentes: Existe preocupación acerca de los efectos cognitivos del consumo de marihuana. Objetivo: Estudiar el efecto de consumo de marihuana presente o pasado en la capacidad de aprendizaje verbal y memoria en una muestra de adultos de 21 años. Material y Métodos: El consumo de marihuana fue evaluado mediante una entrevista médica en 654 adultos de 21 años (56% mujeres), quienes informaron acerca de la frecuencia de consumo, edad de comienzo y si el consumo les ha causado problemas en sus vidas. Se les administró el Cogstate International Shopping List para evaluar aprendizaje y memoria. Resultados: El 70% informó haber consumido marihuana alguna vez, 46% la usó durante el último año y el 27% en los últimos 30 días. Estos últimos tuvieron un menor puntaje en memoria tardía. El consumo actual y frecuente se asoció a una menor precisión en la capacidad de aprendizaje verbal y memoria. Conclusiones: En esta cohorte de adultos de 21 años, el consumo de marihuana fue prevalente y relacionado a una menor memoria verbal.
Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Recuerdo Mental/efectos de los fármacos , Aprendizaje Verbal/efectos de los fármacos , Cannabinoides/farmacología , Uso de la Marihuana/epidemiología , Memoria/efectos de los fármacos , Factores de Tiempo , Chile/epidemiología , Abuso de Marihuana/etiología , Abuso de Marihuana/epidemiología , Estudios Transversales , Trastornos del Conocimiento/complicaciones , Uso de la Marihuana/efectos adversos , Pruebas NeuropsicológicasRESUMEN
The role of the calcium-permeable AMPA receptor (CP-AMPAR) in synaptic plasticity is well established. CP-AMPAR is believed to be recruited to synapse when the memory trace is in a plastic state; however, the direct implications of its expression for memory processes is less known. Here, we investigated the contribution of CP-AMPAR expressed in the basolateral amygdala (BLA) and hippocampus (HPC) in consolidation of different types of memory, retrieval and memory update. We showed that CP-AMPAR blockade by NASPM in the BLA and HPC impaired fear memory consolidation. NASPM infusion in the HPC also impaired spatial memory consolidation in the water maze, whereas consolidation of object location memory was not affected. We found evidence of the CP-AMPAR involvement in the BLA and in the HPC upon memory retrieval. Furthermore, memory update was affected by NASPM infusion in the HPC in both immediate shock deficit and water maze reversal learning tasks. Our data indicate that the activity of CP-AMPAR in the BLA and HPC is required for the consolidation of emotional memories. Moreover, this receptor activity is required for memory retrieval in the BLA and HPC. These findings support that CP-AMPAR has a key function in memory states in which plastic changes are presumably higher, such as the beginning of memory consolidation, and retrieval-induced updating.
Asunto(s)
Consolidación de la Memoria/fisiología , Recuerdo Mental/fisiología , Receptores AMPA/metabolismo , Animales , Complejo Nuclear Basolateral/efectos de los fármacos , Complejo Nuclear Basolateral/metabolismo , Calcio/metabolismo , Antagonistas de Aminoácidos Excitadores/farmacología , Miedo/efectos de los fármacos , Miedo/fisiología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Consolidación de la Memoria/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Ratas Wistar , Receptores AMPA/antagonistas & inhibidores , Aprendizaje Inverso/efectos de los fármacos , Aprendizaje Inverso/fisiología , Memoria Espacial/efectos de los fármacos , Memoria Espacial/fisiología , Espermina/análogos & derivados , Espermina/farmacologíaRESUMEN
The dentate gyrus (DG) is a neurogenic structure that exhibits functional and structural reorganization after injury. Neurogenesis and functional recovery occur after brain damage, and the possible relation between both processes is a matter of study. We explored whether neurogenesis and the activation of new neurons correlated with DG recovery over time. We induced a DG lesion in young adult rats through the intrahippocampal injection of kainic acid and analyzed functional recovery and the activation of new neurons after animals performed a contextual fear memory task (CFM) or a control spatial exploratory task. We analyzed the number of BrdU+ cells that co-localized with doublecortin (DCX) or with NeuN within the damaged DG and evaluated the number of cells in each population that were labelled with the activity marker c-fos after either task. At 10 days post-lesion (dpl), a region of the granular cell layer was devoid of cells, evidencing the damaged area, whereas at 30 dpl this region was significantly smaller. At 10 dpl, the number of BrdU+/DCX+/c-fos positive cells was increased compared to the sham-lesion group, but CFM was impaired. At 30 dpl, a significantly greater number of BrdU+/NeuN+/c-fos positive cells was observed than at 10 dpl, and activation correlated with CFM recovery. Performance in the spatial exploratory task induced marginal c-fos immunoreactivity in the BrdU+/NeuN+ population. We demonstrate that neurons born after the DG was damaged survive and are activated in a time- and task-dependent manner and that activation of new neurons occurs along functional recovery.
Asunto(s)
Giro Dentado/lesiones , Giro Dentado/patología , Recuerdo Mental/fisiología , Neurogénesis/fisiología , Neuronas/fisiología , Animales , Mapeo Encefálico , Bromodesoxiuridina , Condicionamiento Psicológico/efectos de los fármacos , Condicionamiento Psicológico/fisiología , Giro Dentado/diagnóstico por imagen , Proteína Doblecortina , Agonistas de Aminoácidos Excitadores/toxicidad , Conducta Exploratoria/fisiología , Miedo/efectos de los fármacos , Miedo/fisiología , Ácido Kaínico/toxicidad , Masculino , Recuerdo Mental/efectos de los fármacos , Microscopía Confocal , Proteínas del Tejido Nervioso/metabolismo , Neurogénesis/efectos de los fármacos , Neuronas/efectos de los fármacos , Ratas , Ratas Wistar , Conducta Espacial/efectos de los fármacos , Conducta Espacial/fisiología , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
Even though the effects of overtraining and glucocorticoids on different phases of spatial memory are known, the interaction between these factors on the retrieval and extinction of spatial memory has not yet been described. Adult male Wistar rats received eight training trials per day in the Barnes maze for either one or two days. Twenty-four hours after the last training trial they were randomly assigned for receiving an intraperitoneal vehicle or corticosterone injection (0.125 or 0.5â¯mg/kg) and ten minutes later they were given a memory test, followed by seven extinction trials. Extinction retention was evaluated twenty-four hours after extinction. The second training session did not provoke significant changes regarding escape latency nor weighted errors, thereby showing that overtraining had been obtained. The overtrained animals performed better than the trained ones during the retrieval test. Corticosterone administration did not affect the overtrained animals' performance; by contrast, only the lower dose impaired trained animals' retrieval. Overtrained subjects acquired extinction more rapidly than those which received just one session, but corticosterone did not significantly modify extinction. However, whilst the spatial task remained extinguished in trained animals during the extinction retrieval test, spontaneous recovery occurred in overtrained animals. Such training intensity effects on extinction retrieval were reverted by corticosterone. Overall, these results suggested that overtraining modified the susceptibility of spatial memory's trace to the effects of corticosterone on retrieval and extinction.
Asunto(s)
Corticosterona/administración & dosificación , Extinción Psicológica/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Memoria Espacial/efectos de los fármacos , Animales , Masculino , Aprendizaje por Laberinto , Ratas Wistar , Aprendizaje EspacialRESUMEN
It is well known that stress can affect mnemonic processes. In particular, stress before contextual fear conditioning induces a memory which exhibits resistance to being interfered with by Midazolam (MDZ) when applied after memory retrieval. Moreover, stress exposure strongly affects GABAergic transmission within the Basolateral Amygdala Complex (BLA), a brain structure critically involved in fear memory processing. The present study evaluated the involvement of GABAergic signaling within the BLA on the induction of resistance to memory reconsolidation interference. Results showed that MDZ administered intra-BLA before stress prevented the induction of resistance to the interfering effect of systemic administration of both MDZ and Propranolol on fear memory reconsolidation, when both applied after memory retrieval. The blockade of amygdala GABA-A receptors by the antagonist Bicuculline (BIC) before memory encoding induced resistance to interference by post-recall MDZ administration, similarly to that observed with stress exposure. Additionally, the systemic administration of d-cycloserine, a positive allosteric modulator of NMDA receptor, reverted the BIC-induced resistance to the MDZ interfering effect, in the same manner as that reported with stress-induced resistance. In summary, these results suggest that the GABAergic signaling in the BLA at the moment of memory encoding is determinant for the induction of fear memory resistance to the onset of the labilization/reconsolidation process.
Asunto(s)
Complejo Nuclear Basolateral/fisiología , Miedo , Consolidación de la Memoria/fisiología , Recuerdo Mental/fisiología , Estrés Psicológico , Ácido gamma-Aminobutírico/fisiología , Antagonistas Adrenérgicos beta/administración & dosificación , Animales , Reacción de Prevención/efectos de los fármacos , Complejo Nuclear Basolateral/efectos de los fármacos , Moduladores del GABA/administración & dosificación , Masculino , Consolidación de la Memoria/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Midazolam/administración & dosificación , Propranolol/administración & dosificación , Ratas WistarRESUMEN
It is well established that corticosterone (CORT) enhances memory consolidation of emotionally arousing experiences. Despite emotional memories being usually referred to as well remembered for long periods, there are no studies that have investigated the effects of CORT in modulating the duration and specificity of memory. In the present study, we trained Wistar rats in a single-trial contextual fear conditioning protocol and injected CORT (0.3, 1.0 or 3.0mg/kg), immediately after training, to investigate its effects on memory consolidation. Rats were tested 2 and 29days after the training session or only 29days after training to assess recent or remote memory. Our results show that animals tested for recent memory discriminated the training context from a novel one, while those tested only for remote memory generalized the fear response to both contexts. Animals tested for remote memory after being tested for recent memory were able to discriminate both contexts. These results support the literature regarding memory specificity and duration. However, CORT treatment, even at the dose of 1.0mg/kg that effectively enhanced the plasmatic hormone levels, did not affect the strength or the specificity of memory in either recent or remote memory tests. We hypothesize that the lack of effect of CORT treatment could be due to the low arousing training experience of the single-trial protocol which, despite being sufficient to induce significant recent and remote memory consolidation, may not be sufficient to allow the memory-enhancing effect of CORT.
Asunto(s)
Antiinflamatorios/administración & dosificación , Condicionamiento Clásico/efectos de los fármacos , Corticosterona/administración & dosificación , Miedo/efectos de los fármacos , Memoria a Largo Plazo/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Análisis de Varianza , Animales , Antiinflamatorios/sangre , Corticosterona/sangre , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the gustatory zone of the IC during CTA retrieval. Additionally, it has been reported that the amygdala-IC interaction is highly involved in CTA memory establishment. Therefore, we evaluated the effects of infusions of an AMPA receptor antagonist (CNQX) and a NMDA receptor antagonist (APV) into the amygdala on CTA retrieval and IC neurotransmitter levels. Infusion of APV into the amygdala impaired glutamate augmentation within the IC, whereas dopamine and norepinephrine levels augmentation persisted and a reliable CTA expression was observed. Conversely, CNQX infusion into the amygdala impaired the aversion response, as well as norepinephrine and dopamine augmentations in the IC. Interestingly, CNQX infusion did not affect glutamate elevation in the IC. To evaluate the functional meaning of neurotransmitters elevations within the IC on CTA response, we infused specific antagonists for the AMPA, NMDA, D1, and ß-adrenergic receptor before retrieval. Results showed that activation of AMPA, D1, and ß-adrenergic receptors is necessary for CTA expression, whereas NMDA receptors are not involved in the aversion response.
Asunto(s)
Amígdala del Cerebelo/metabolismo , Reacción de Prevención/fisiología , Corteza Cerebral/fisiología , Recuerdo Mental/fisiología , Vías Nerviosas/fisiología , Receptores de Glutamato/metabolismo , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Dopamina/metabolismo , Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Glutámico/metabolismo , Masculino , Recuerdo Mental/efectos de los fármacos , Vías Nerviosas/efectos de los fármacos , Norepinefrina/metabolismo , Ratas , Ratas Wistar , Gusto/efectos de los fármacos , Gusto/fisiología , Valina/análogos & derivados , Valina/farmacologíaRESUMEN
Several studies have investigated the transition of consolidation of recent memory to remote memory in aversively motivated tasks, such as contextual fear conditioning (CFC) and inhibitory avoidance (IA). However, the mechanisms that serve the retrieval of remote memories, has not yet been fully understood. Some evidences suggest that the central cholinergic system appears be involved in the modulation of these processes. Therefore, the present study aimed to investigate the effects of a pre-test administration of dicyclomine, a high-affinity M1 muscarinic receptor antagonist, on the retrieval of remote memories in fear conditioning and IA tasks. Male Wistar rats were trained, and after 1 or 28days, the rats received dicyclomine (16 or 32mg/kg, intraperitoneally, i.p.) and were tested in CFC, tone fear conditioning (TFC) and IA tasks. At both time intervals, 32mg/kg dicyclomine induced impairment of CFC. In TFC task only the performance of the rats 28days after training was impaired. The IA task was not affected in any of the studied intervals. These findings suggest a differential contribution of muscarinic receptors on recent and remote memories retrieval revealing a more generalized role in remote memory.
Asunto(s)
Reacción de Prevención/fisiología , Condicionamiento Clásico/fisiología , Miedo/fisiología , Recuerdo Mental/fisiología , Receptor Muscarínico M1/metabolismo , Estimulación Acústica/efectos adversos , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Diciclomina/farmacología , Relación Dosis-Respuesta a Droga , Miedo/efectos de los fármacos , Masculino , Recuerdo Mental/efectos de los fármacos , Antagonistas Muscarínicos/farmacología , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
In addicts, craving and relapse are frequently induced by the recall of memories related to a drug experience. Several studies have demonstrated that drug-related memories are reactivated after exposure to environmental cues and may undergo reconsolidation, a process that can strengthen memories. Thus, reactivation of mnemonic traces provides an opportunity for disrupting memories that contribute to the pathological cycle of addiction. Here we used drug-induced conditioned place preference (CPP) to investigate whether cannabidiol (CBD), a phytocannabinoid, given just after reactivation sessions, would affect reconsolidation of drug-reward memory, reinstatement of morphine-CPP, or conditioned place aversion precipitated by naltrexone in Wistar rats. We found that CBD impaired the reconsolidation of preference for the environment previously paired with both morphine and cocaine. This disruption seems to be persistent, as the preference did not return after further reinstatement induced by priming drug and stress reinstatement. Moreover, in an established morphine-CPP, an injection of CBD after the exposure to a conditioning session led to a significant reduction of both morphine-CPP and subsequent conditioned place aversion precipitated by naltrexone in the same context. Thus, established memories induced by a drug of abuse can be blocked after reactivation of the drug experience. Taken together, these results provide evidence for the disruptive effect of CBD on reconsolidation of contextual drug-related memories and highlight its therapeutic potential to attenuate contextual memories associated with drugs of abuse and consequently to reduce the risk of relapse.