RESUMO
Extinction is the learned inhibition of retrieval of a previously acquired memory and is a major component of exposure therapy, which has attracted much attention because of the use in the treatment of drug addiction, phobias and particularly fear disorders such as post-traumatic stress disorder (PTSD). Exposure to a novel environment before or after extinction training can enhance the extinction of contextual fear conditioning, however the cellular and molecular substrates are still unclear. Here, we investigated the participation of H2-histaminergic, ß-adrenergic and 5-HT1A-serotonergic receptors of the hippocampus on the enhancement of extinction memory caused by novelty. The infusion into the CA1 region of the serotonin 5-HT1A-receptor agonist, 8-OH-DPAT and the ß-adrenergic blocker, Timolol, after the exposure to the novelty hindered the enhancement of extinction by novelty, while Timolol also hindered the extinction consolidation when infused post-extinction. These impairments were abolished by the coinfusion of 8-OH-DPAT plus the 5-HT1A receptor antagonist, NAN-190 and Timolol plus ß-adrenergic agonist, Isoproterenol. However, Dimaprit and Ranitidine blocked the retrieval of CFC, but did not prevented the extinction learning. Here we elucidated some of the molecular mechanisms that are involved on the enhancement of extinction by novelty, demonstrating that the ß-adrenoreceptors and 5-HT1A serotonergic receptors participate on this process alongside with dopaminergic D1 receptors previously described, while histamine H2 receptors, so ubiquitous in learning-related functions in hippocampus are not involved.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Aprendizagem por Associação/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Condicionamento Clássico/efeitos dos fármacos , Isoproterenol/farmacologia , Masculino , Ratos Wistar , Timolol/farmacologiaRESUMO
The process of memory formation is complex and highly dynamic. During learning, the newly acquired information is found in a fragile and labile state. Through a process known as consolidation, which requires specific mechanisms such as protein synthesis, the memory trace is stored and stabilized. It is known that when a consolidated memory is recalled, it again becomes labile and sensitive to disruption. To be maintained, this memory must undergo an additional process of restabilization called reconsolidation, which requires another phase of protein synthesis. Memory consolidation has been studied for more than a century, while the molecular mechanisms underlying the memory reconsolidation are starting to be elucidated. For this, is essential compare the participation of important neurotransmitters and its receptors in both processes in brain regions that play a central role in the fear response learning. With focus on serotonin (5-HT), a well characterized neurotransmitter that has been strongly implicated in learning and memory, we investigated, in the CA1 region of the dorsal hippocampus, whether the latest discovered serotonergic receptors, 5-HT5A, 5-HT6 and 5-HT7, are involved in the consolidation and reconsolidation of contextual fear conditioning (CFC) memory. For this, male rats with cannulae implanted in the CA1 region received immediately after the training or reactivation session, or 3h post-reactivation of the CFC, infusions of agonists or antagonists of the 5-HT5A, 5-HT6 and 5-HT7 receptors. After 24h, animals were subjected to a 3-min retention test. The results indicated that in the CA1 region of the hippocampus the 5-HT5A, 5-HT6 and 5-HT7 serotonin receptors participate in the reconsolidation of the CFC memory 3h post-reactivation. Additionally, the results suggest that the 5-HT6 and 5-HT7 receptors also participate in the consolidation of the CFC memory.
Assuntos
Medo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Memória/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Animais , Condicionamento Clássico/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
Pituitary adenylate cyclase-activating polypeptide (PACAP) has a broad spectrum of biological functions including neurotransmitter, neurotrophic and neuroprotective. Moreover, it has been suggested that PACAP plays a role in the modulation of learning and memory as well as on the modulation of glutamate signaling. Thus, in the current study we investigated in the CA1 region of hippocampus and in the basolateral amygdala (BLA) the role of PACAP in the consolidation and extinction of contextual fear conditioning (CFC) and the interaction between PACAP and NMDA receptors. Male rats with cannulae implanted in the CA1 region of the hippocampus or in the BLA received immediately after the training or extinction training of the CFC infusions of the Vehicle, PACAP-38 (40 pg/side), PACAP 6-38 (40 pg/side) or PACAP 6-38 plus D-serine (50 µg/side). After 24h, the animals were subjected to a 3-min retention test. The results indicated that in the CA1 region of hippocampus, PACAP participates in the consolidation and extinction of the CFC, and in the BLA, PACAP participates only in the consolidation of the CFC. Additionally, the results suggest that the action of PACAP on the consolidation and extinction of the CFC is mediated by the glutamate NMDA receptors.
Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Região CA1 Hipocampal/fisiologia , Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Ratos , Ratos WistarRESUMO
Early-life environmental events, such as the handling procedure, can induce long-lasting alterations upon several behavioral and neuroendocrine systems. However, the changes within the pups that could be causally related to the effects in adulthood are still poorly understood. In the present study, we analyzed the effects of neonatal handling on behavioral (maternal odor preference) and biochemical (cyclic AMP response element-binding protein (CREB) phosphorylation, noradrenaline (NA), and serotonin (5-HT) levels in the olfactory bulb (OB)) parameters in 7-day-old male and female rat pups. Repeated handling (RH) abolished preference for the maternal odor in female pups compared with nonhandled (NH) and the single-handled (SH) ones, while in RH males the preference was not different than NH and SH groups. In both male and female pups, RH decreased NA activity in the OB, but 5-HT activity increased only in males. Since preference for the maternal odor involves the synergic action of NA and 5-HT in the OB, the maintenance of the behavior in RH males could be related to the increased 5-HT activity, in spite of reduction in the NA activity in the OB. RH did not alter CREB phosphorylation in the OB of both male and females compared with NH pups. The repeated handling procedure can affect the behavior of rat pups in response to the maternal odor and biochemical parameters related to the olfactory learning mechanism. Sex differences were already detected in 7-day-old pups. Although the responsiveness of the hypothalamic-pituitary-adrenal axis to stressors is reduced in the neonatal period, environmental interventions may impact behavioral and biochemical mechanisms relevant to the animal at that early age.
Assuntos
Monoaminas Biogênicas/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Manobra Psicológica , Comportamento Materno , Odorantes , Bulbo Olfatório/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Cromatografia Líquida de Alta Pressão/métodos , Condicionamento Psicológico , Eletroquímica/métodos , Feminino , Masculino , Gravidez , Ratos , Ratos Wistar , Fatores Sexuais , Transdução de Sinais/fisiologiaRESUMO
Storage of acetylcholine in synaptic vesicles plays a key role in maintaining cholinergic function. Here we used mice with a targeted mutation in the vesicular acetylcholine transporter (VAChT) gene that reduces transporter expression by 40% to investigate cognitive processing under conditions of VAChT deficiency. Motor skill learning in the rotarod revealed that VAChT mutant mice were slower to learn this task, but once they reached maximum performance they were indistinguishable from wild-type mice. Interestingly, motor skill performance maintenance after 10 days was unaffected in these mutant mice. We also tested whether reduced VAChT levels affected learning in an object recognition memory task. We found that VAChT mutant mice presented a deficit in memory encoding necessary for the temporal order version of the object recognition memory, but showed no alteration in spatial working memory, or spatial memory in general when tested in the Morris water maze test. The memory deficit in object recognition memory observed in VAChT mutant mice could be reversed by cholinesterase inhibitors, suggesting that learning deficits caused by reduced VAChT expression can be ameliorated by restoring ACh levels in the synapse. These data indicate an important role for cholinergic tone in motor learning and object recognition memory.
Assuntos
Deficiências da Aprendizagem/genética , Proteínas Vesiculares de Transporte de Acetilcolina/biossíntese , Proteínas Vesiculares de Transporte de Acetilcolina/genética , Animais , Relação Dose-Resposta a Droga , Imunofluorescência , Deficiências da Aprendizagem/psicologia , Aprendizagem em Labirinto/fisiologia , Rememoração Mental/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Atividade Motora/fisiologia , Destreza Motora/fisiologia , Terminações Nervosas/metabolismo , Equilíbrio Postural/fisiologia , Desempenho Psicomotor/fisiologia , Reconhecimento Psicológico/fisiologiaRESUMO
BACKGROUND: With the current increasing incidence of allergies worldwide, new treatments showing efficacy and long term safety are needed for chronic conditions such as persistent allergic rhinitis (PER). New generation H1-antihistamines have demonstrated anti-allergic properties, which could possibly enhance their effectiveness in long-term periods of treatment. OBJECTIVE: To investigate the efficacy of rupatadine, in controlling symptoms of PER over a 12-week period. METHODS: A randomized, double blind, parallel-group, placebo-controlled study was carried out in patients aged older than 12 years with PER. Main inclusion criteria were: instantaneous total symptom score (i6TSS) >or=45, nasal obstruction score
Assuntos
Antialérgicos/uso terapêutico , Cetirizina/uso terapêutico , Ciproeptadina/análogos & derivados , Rinite Alérgica Perene/tratamento farmacológico , Adolescente , Adulto , Antialérgicos/administração & dosagem , Antialérgicos/efeitos adversos , Cetirizina/administração & dosagem , Cetirizina/efeitos adversos , Ciproeptadina/administração & dosagem , Ciproeptadina/efeitos adversos , Ciproeptadina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Memory consolidation involves a sequence of temporally defined and highly regulated changes in the activation state of several signaling pathways that leads to the lasting storage of an initially labile trace. Despite appearances, consolidation does not make memories permanent. It is now known that upon retrieval well-consolidated memories can become again vulnerable to the action of amnesic agents and in order to persist must undergo a protein synthesis-dependent process named reconsolidation. Experiments with genetically modified animals suggest that some PKC isoforms are important for spatial memory and earlier studies indicate that several PKC substrates are activated following spatial learning. Nevertheless, none of the reports published so far analyzed pharmacologically the role played by PKC during spatial memory processing. Using the conventional PKC and PKCmu inhibitor 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrollo[3,4-c]carbazole (Gö6976) we found that the activity of these kinases is required in the CA1 region of the rat dorsal hippocampus for acquisition and consolidation of spatial memory in the Morris water maze learning task. Our results also show that when infused into dorsal CA1 after non-reinforced retrieval, Gö6976 produces a long-lasting amnesia that is independent of the strength of the memory trace, suggesting that post-retrieval activation of hippocampal PKC is essential for persistence of spatial memory.
Assuntos
Hipocampo/enzimologia , Aprendizagem em Labirinto/fisiologia , Rememoração Mental/fisiologia , Proteína Quinase C/metabolismo , Percepção Espacial/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Carbazóis/administração & dosagem , Esquema de Medicação , Inibidores Enzimáticos/administração & dosagem , Hipocampo/efeitos dos fármacos , Indóis/administração & dosagem , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Microinjeções , Proteína Quinase C/antagonistas & inibidores , Ratos , Ratos Wistar , Percepção Espacial/efeitos dos fármacosRESUMO
Nicotine is the main alkaloid of tobacco and possesses well-established stimulant effects. Previous reports show that nicotine at low doses improves memory functions, while high doses impair memory. This study aims to analyze the effects of nicotine (NIC) on inhibitory avoidance task and on DNA damage, reactive oxygen species (ROS) concentration, total antioxidant capacity, and lipid peroxidation in cortex and hippocampus of old rats. Male Wistar rats of 24-26 months old (620-700g) were exposed i.p. to two doses (0.3 and 1mg/kg) of NIC daily during 9 days. The treatment NIC 0.3 enhanced long-term memory (p<0.05), whereas NIC 1 improved both short and long-term memories (p<0.05). DNA damage was observed only in hippocampus (p<0.05) after NIC 1 exposure. A similar result was obtained for ROS: higher levels were detected at NIC 1 treatment in hippocampus (p<0.05). No alterations in the total antioxidant capacity were verified after NIC exposure (0.3 and 1mg/kg) in both tissues (p>0.05). Finally, evidence of oxidative damage was observed in terms of lipid peroxides levels, being higher at NIC 1 in hippocampus (p<0.05). Overall the results indicate that deleterious effects paralleled the improved short and long-term memories at the highest NIC dose, since augmented DNA damage, ROS concentration and lipid peroxides levels were registered.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/crescimento & desenvolvimento , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Nicotina/farmacologia , Nicotina/toxicidade , Agonistas Nicotínicos/farmacologia , Agonistas Nicotínicos/toxicidade , Animais , Antioxidantes/metabolismo , Aprendizagem da Esquiva/efeitos dos fármacos , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Sequestradores de Radicais Livres/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/metabolismo , Memória/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Two major memory systems have been recognized over the years (Squire, in Memory and Brain, 1987): the declarative memory system, which is under the control of the hippocampus and related temporal lobe structures, and the procedural or habit memory system, which is under the control of the striatum and its connections (Mishkin et al., in Neurobiology of Learning by G Lynch et al., 1984; Knowlton et al., Science 273:1399, 1996). Most if not all learning tasks studied in animals, however, involve either the performance or the suppression of movement. Animals acquire connections between environmental or discrete sensory cues (conditioned stimuli, CSs) and emotionally or otherwise significant stimuli (unconditioned stimuli, USs). As a result, they learn to perform or to inhibit the performance of certain motor responses to the CS which, when learned well, become what can only be called habits (Mishkin et al., 1984): to regularly walk or swim to a place or away from a place, or to inhibit one or several forms of movement. These responses can be viewed as conditioned responses (CRs) and may sometimes be very complex. This is of course also seen in humans: people learn how to play on a keyboard in response to a mental or written script and perform the piano or write a text; with practice, the performance improves and eventually reaches a high criterion and becomes a habit, performed almost if not completely without awareness. Commuting to school in a big city in the shortest possible time and eschewing the dangers is a complex learning that children acquire to the point of near-perfection. It is agreed that the rules that connect the perception of the CS and the expression of the CR change from their first association to those that take place when the task is mastered. Does this change of rules involve a switch from one memory system to another? Are different brain systems used the first time one plays a sonata or goes to school as compared with the 100th time? Here we will comment on: 1) reversal learning in the Morris water maze (MWM), in which the declarative or spatial component of a task is changed but the procedural component (to swim) persists and needs to be re-linked with a different set of spatial cues; and 2) a series of observations on an inhibitory avoidance task that indicate that the brain systems involved change with further learning.
Assuntos
Corpo Estriado/fisiologia , Hipocampo/fisiologia , Memória , Vias Neurais/fisiologia , Animais , Aprendizagem da Esquiva/fisiologia , Humanos , Aprendizagem em LabirintoRESUMO
Inhibitory avoidance (IA) learning relies on the formation of an association between stepping down from a platform present in a certain context (conditioned stimulus; CS) with an aversive unconditioned stimulus (US; i.e. a footshock). A single CS-US pairing establishes a robust long-term memory expressed as an increase in step-down latency at testing. However, repeated retrieval of the avoidance response in the absence of the US induces extinction of IA memory. That is, recurring presentation of the CS alone results in a new learning indicating that the CS no longer predicts the US. Although the signaling pathways involved in the consolidation of IA and other fear-motivated memories have been profusely studied, little is known about the molecular requirements of fear memory extinction. Here we report that, as happens with its consolidation, extinction of IA long-term memory requires activity of the p38 subfamily of mitogen-activated protein kinases (MAPK) in the CA1 region of the dorsal hippocampus. Moreover, we found that inhibition of hippocampal p38MAPK blocked memory reacquisition after extinction without affecting either the increase in IA memory retention induced by a second training session or animal's locomotor/exploratory activity and anxiety state.
Assuntos
Aprendizagem da Esquiva/fisiologia , Extinção Psicológica/fisiologia , Hipocampo/enzimologia , Inibição Psicológica , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Imidazóis/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Piridinas/farmacologia , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Fatores de TempoRESUMO
Although the gastrin-releasing peptide-preferring bombesin receptor (GRPR) has been implicated in memory formation, the underlying molecular events are poorly understood. In the present study, we examined interactions between the GRPR and cellular signaling pathways in influencing memory consolidation in the hippocampus. Male Wistar rats received bilateral infusions of bombesin (BB) into the dorsal hippocampus immediately after inhibitory avoidance (IA) training. Intermediate doses of BB enhanced, whereas a higher dose impaired, 24-h IA memory retention. The BB-induced memory enhancement was prevented by pretraining infusions of a GRPR antagonist or inhibitors of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) kinase and protein kinase A (PKA), but not by a neuromedin B receptor (NMBR) antagonist. We next further investigated the interactions between the GRPR and the PKA pathway. BB-induced enhancement of consolidation was potentiated by coinfusion of activators of the dopamine D1/D5 receptor (D1R)/cAMP/PKA pathway and prevented by a PKA inhibitor. We conclude that memory modulation by hippocampal GRPRs is mediated by the PKC, MAPK, and PKA pathways. Furthermore, pretraining infusion of BB prevented beta-amyloid peptide (25-35)-induced memory impairment, supporting the view that the GRPR is a target for the development of cognitive enhancers for dementia.
Assuntos
Hipocampo/fisiologia , Memória , Receptores da Bombesina/fisiologia , Peptídeos beta-Amiloides/farmacologia , Animais , Bombesina/farmacologia , AMP Cíclico/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Hipocampo/efeitos dos fármacos , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/fisiologia , Fragmentos de Peptídeos/farmacologia , Proteína Quinase C/fisiologia , Ratos , Ratos Wistar , Receptores da Bombesina/agonistas , Receptores de Dopamina D5/agonistas , Transdução de SinaisRESUMO
We studied the effects of infusion of nerve growth factor (NGF) into the hippocampus and entorhinal cortex of male Wistar rats (250-300 g, N = 11-13 per group) on inhibitory avoidance retention. In order to evaluate the modulation of entorhinal and hippocampal NGF in short- and long-term memory, animals were implanted with cannulae in the CA1 area of the dorsal hippocampus or entorhinal cortex and trained in one-trial step-down inhibitory avoidance (foot shock, 0.4 mA). Retention tests were carried out 1.5 h or 24 h after training to measure short- and long-term memory, respectively. Immediately after training, rats received 5 microl NGF (0.05, 0.5 or 5.0 ng) or saline per side into the CA1 area and entorhinal cortex. The correct position of the cannulae was confirmed by histological analysis. The highest dose of NGF (5.0 ng) into the hippocampus blocked short-term memory (P < 0.05), whereas the doses of 0.5 (P < 0.05) and 5.0 ng (P < 0.01) NGF enhanced long-term memory. NGF administration into the entorhinal cortex improved long-term memory at the dose of 5.0 ng (P < 0.05) and did not alter short-term memory. Taken as a whole, our results suggest a differential modulation by entorhinal and hippocampal NGF of short- and long-term memory.
Assuntos
Córtex Entorrinal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Fator de Crescimento Neural/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Córtex Entorrinal/fisiologia , Hipocampo/fisiologia , Masculino , Memória/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Ratos , Ratos Wistar , Retenção Psicológica/efeitos dos fármacosRESUMO
We studied the effects of infusion of nerve growth factor (NGF) into the hippocampus and entorhinal cortex of male Wistar rats (250-300 g, N = 11-13 per group) on inhibitory avoidance retention. In order to evaluate the modulation of entorhinal and hippocampal NGF in short- and long-term memory, animals were implanted with cannulae in the CA1 area of the dorsal hippocampus or entorhinal cortex and trained in one-trial step-down inhibitory avoidance (foot shock, 0.4 mA). Retention tests were carried out 1.5 h or 24 h after training to measure short- and long-term memory, respectively. Immediately after training, rats received 5 æl NGF (0.05, 0.5 or 5.0 ng) or saline per side into the CA1 area and entorhinal cortex. The correct position of the cannulae was confirmed by histological analysis. The highest dose of NGF (5.0 ng) into the hippocampus blocked short-term memory (P < 0.05), whereas the doses of 0.5 (P < 0.05) and 5.0 ng (P < 0.01) NGF enhanced long-term memory. NGF administration into the entorhinal cortex improved long-term memory at the dose of 5.0 ng (P < 0.05) and did not alter short-term memory. Taken as a whole, our results suggest a differential modulation by entorhinal and hippocampal NGF of short- and long-term memory.
Assuntos
Animais , Masculino , Ratos , Córtex Entorrinal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Fator de Crescimento Neural/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Córtex Entorrinal/fisiologia , Hipocampo/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Memória/fisiologia , Ratos Wistar , Retenção Psicológica/efeitos dos fármacosRESUMO
The role of oxidative stress in electroconvulsive therapy-related effects is not well studied. The purpose of this study was to determine oxidative stress parameters in several brain structures after a single electroconvulsive seizure or multiple electroconvulsive seizures. Rats were given either a single electroconvulsive shock or a series of eight electroconvulsive shocks. Brain regions were isolated, and levels of oxidative stress in the brain tissue (cortex, hippocampus, striatum and cerebellum) were measured. We demonstrated a decrease in lipid peroxidation and protein carbonyls in the hippocampus, cerebellum, and striatum several times after a single electroconvulsive shock or multiple electroconvulsive shocks. In contrast, lipid peroxidation increases both after a single electroconvulsive shock or multiple electroconvulsive shocks in cortex. In conclusion, we demonstrate an increase in oxidative damage in cortex, in contrast to a reduction of oxidative damage in hippocampus, striatum, and cerebellum.
Assuntos
Encéfalo/patologia , Eletrochoque/efeitos adversos , Animais , Encéfalo/metabolismo , Cerebelo/patologia , Córtex Cerebral/patologia , Corpo Estriado/patologia , Hipocampo/patologia , Masculino , Especificidade de Órgãos , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
One-trial step-down inhibitory avoidance in rats involves the activation of two separate memory types, a short-term system (STM) that lasts 3-6 h, and a long-term system (LTM) that takes 3-6 h to be formed and lasts for many days or even months. Here we investigate the effect of nicotinic receptor (nAChR) ligands infused bilaterally in the hippocampus on STM and LTM formation and on LTM retrieval of this task. Rats were implanted with chronic cannulae in the CA1 region of the dorsal hippocampus, trained using a 0.5 mA foot shock, and tested twice, first 1.5 h after training to measure STM, and again at 24 h to measure LTM. The drugs used were the nAChR antagonists, mecamylamine (1, 3 and 10 microg/side) and dihydro-beta-erythroidine (DHbetaE; 2, 6 and 18 microg/side) and the agonist, nicotine (0.6, 1 and 3 microg/side). They were given either 15 min before training, immediately after training or 15 min prior to LTM retrieval. Mecamylamine and DHbetaE impaired and nicotine enhanced STM, LTM and retrieval similarly. The results indicate that nAChRs in CA1 participate in the regulation of both STM and LTM formation, and on the retrieval of LTM.
Assuntos
Aprendizagem da Esquiva/fisiologia , Hipocampo/metabolismo , Memória/fisiologia , Receptores Nicotínicos/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Agonistas Nicotínicos/administração & dosagem , Antagonistas Nicotínicos/administração & dosagem , Ratos , Ratos Wistar , Receptores Nicotínicos/efeitos dos fármacosRESUMO
Using 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-D]pyrimidine (PP2), a specific inhibitor of the Src family of tyrosine kinases, here we show a direct involvement of these enzymes in memory formation and recall. When infused into the CA1 region of the dorsal hippocampus, immediately or 30 min after training rats in a one-trial inhibitory avoidance task, PP2 but not its inactive analog 4-amino-7-phenylpyrazol[3,4-D]pyrimidine (PP3), blocked short- (STM) and long-term memory (LTM) formation, as tested 2 or 24 h post-training, respectively. PP2 had no effect on STM when given at 60 min post-training or on LTM when administered at 60, 120 or 180 min after the training session, but blocked memory recall when infused into CA1 15 min before a LTM expression test. Hence, activity of the Src family of tyrosine kinases is required in the CA1 region of the rat dorsal hippocampus for the normal formation and retrieval of one-trial inhibitory avoidance memory.
Assuntos
Aprendizagem da Esquiva , Rememoração Mental/fisiologia , Quinases da Família src/farmacologia , Animais , Hipocampo/fisiologia , Masculino , Ratos , Ratos WistarRESUMO
Several lines of evidence suggest that glutamate receptors are involved in memory processing. To examine the role of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors on memory consolidation, rats were bilaterally implanted with cannulae aimed at the CA1 region of the dorsal hippocampus (CA1), entorhinal cortex (ENTO), posterior parietal cortex (PPC) or the basolateral nucleus of the amygdala (BLA), and trained in a one-trial step-down inhibitory avoidance task. At different times after training, the alpha-amino 3-hydroxy-5 methyl 4-isoxazole propionate (AMPA) receptor blocker, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (1.0 microg/side), or the metabotropic type-I receptor antagonist, 2-amino-3-phosphonopropionic acid (AP3) (1.0 microg/side), were infused into the above-mentioned structures. CNQX produced retrograde amnesia when infused into BLA or CA1 0, 30, 90 or 180 min post-training but not at later times. AP3 blocked memory consolidation when administered into CA1 0, 30 or 180 min post-training, while in BLA, it was amnestic only when given 0 or 30 min after the training session. CNQX and AP3 had no effect on memory when administered into ENTO or PPC at any time. Our data suggest that the consolidation of the avoidance memory requires intact non-NMDA receptor function in the hippocampus and the basolateral nucleus of the amygdala, but not necessarily in the entorhinal and parietal cortex, for long periods after training.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Caínico/farmacologia , Memória/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Córtex Entorrinal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Lobo Parietal/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The objective of our study was to assess the response of physical (aggregate stability and bulk density) and biological (enzyme activities and microbial biomass) soil quality indicators to the adoption of agroecological management practices, such as the planting of forage species (forage area) and the rotation of local crops (polycrop area), carried out in a representative tropical pasture on an integrated livestock-crop farm. The pasture system was used as control (pasture area). In all three areas, the values of water-soluble C were higher in the rainy season compared to the dry season. Pasture and forage areas had the highest percentage of stable aggregates in the rainy season, while polycrops developed soils with less stable aggregates. Soil bulk density was lower in the pasture and forage areas than in the polycrop area. In the pasture area, the microbial biomass C values, dehydrogenase, urease, protease-BAA, acid phosphatase, and beta-glucosidase activities were higher than in the forage and polycrop areas, particularly in the dry season. The highest increase in the microbial biomass C in the rainy season, with respect to the dry season, was recorded in the pasture area (about 1.2-fold). In conclusion, the planting of forage species can be considered an effective practice for carrying out sustainable, integrated livestock-crop systems, due to its general maintenance of soil quality, while the adoption of polycrop rotations appears to be less favorable because it decreases soil quality.
Assuntos
Agricultura , Microbiologia do Solo , Solo , Biomassa , Cuba , Monitoramento Ambiental , Poaceae/crescimento & desenvolvimento , Controle de Qualidade , Estações do Ano , Clima TropicalRESUMO
It has been known for years that systemic administration of the stress hormones, adrenocorticotrophin (ACTH), lysine-vasopressin, adrenaline, or beta-endorphin, enhances retrieval of aversive behaviours acquired one or a few days before. Here we show that the pre-test i.p. injection of the hormones in rats can also enhance retrieval when given months after the original training. The effectiveness of the treatments changed with time. When animals were tested 3 months after training the hormones enhanced retrieval only at doses five times higher than those needed 1 day after training. Between 6 and 9 months from training the hormones either lost their effect (vasopressin, beta-endorphin) or actually inhibited retrieval (ACTH, adrenaline). The effects of the hormones cannot be explained by a decrease in locomotor activity: none of the treatments had such an effect, as measured in an open field. However, when the animals were tested between 12 and 19 months after training, the hormones once again became as effective as they had been 1 day after training. This was so in spite of the fact that control retention levels became very low with age, probably as a result of extinction. The oscillation of the sensitivity of retrieval to the hormones does not appear to depend on changes in anxiety levels with ageing or to effects of the hormones on locomotor activity.
Assuntos
Condicionamento Psicológico/efeitos dos fármacos , Medo/efeitos dos fármacos , Hormônios/farmacologia , Memória/efeitos dos fármacos , Estresse Psicológico/fisiopatologia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Ansiedade/psicologia , Aprendizagem da Esquiva/efeitos dos fármacos , Eletrochoque , Epinefrina/farmacologia , Extinção Psicológica/efeitos dos fármacos , Lipressina/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , beta-Endorfina/farmacologiaRESUMO
Wistar rats were trained in step-down inhibitory avoidance at the age of 3 months, and tested for retrieval either 1 day later or 3, 6, 9, 12, 15 or 19 months later, when the animals were 6, 9, 12, 15, 18 or 22 months old, respectively. Bupropion (20 or 60 mg/kg) and sertraline (3.3 or 10 mg/kg) given orally 6 or 3 h before retention testing, respectively, enhanced retrieval of this task at all training-test intervals, despite the fact that retrieval at the longest intervals was practically not seen in control animals. The effect cannot be explained by influences of the drugs on locomotor activity; the treatments had no effect on open field behaviour at the age of 3, 8 or 21 months. The findings may be relevant to the use of these drugs as cognitive enhancers in elderly subjects.