RESUMEN
The lesions induced by Ibotenic acid (IA) emulate some of the symptoms associated with schizophrenia, such as impaired working memory that is predominantly organized by the medial prefrontal cortex (mPFC), or difficulties in social interactions that aremainly organized by the amygdala (AMG). The plastic capacity of dendritic spines in neurons of the mPFC and AMG is modulated by molecules that participate in the known deterioration of working memory, although the influence of these on the socialization of schizophrenic patients is unknown. Here, the effect of a neonatal IA induced lesion on social behavior and working memory was evaluated in adult rats, along with the changes in cytoarchitecture of dendritic spines and their protein content, specifically the postsynaptic density protein 95 (PSD-95), Synaptophysin (Syn), AMPA receptors, and brain-derived neurotrophic factor (BDNF). Both working memory and social behavior were impaired, and the density of the spines, as well as their PSD-95, Syn, AMPA receptor and BDNF content was lower in IA lesioned animals. The proportional density of thin, mushroom, stubby and wide spines resulted in plastic changes that suggest the activation of compensatory processes in the face of the adverse effects of the lesion. In addition, the reduction in the levels of the modulating factors also suggests that the signaling pathways in which such factors are implicated would be altered in the brains of patients with schizophrenia. Accordingly, the experimental study of such signaling pathways is likely to aid the development of more effective pharmacological strategies for the treatment of schizophrenia.
Asunto(s)
Amígdala del Cerebelo/patología , Conducta Animal , Espinas Dendríticas/patología , Plasticidad Neuronal , Corteza Prefrontal/patología , Esquizofrenia/patología , Psicología del Esquizofrénico , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/fisiopatología , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Espinas Dendríticas/metabolismo , Modelos Animales de Enfermedad , Homólogo 4 de la Proteína Discs Large/metabolismo , Ácido Iboténico , Masculino , Aprendizaje por Laberinto , Memoria a Corto Plazo , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiopatología , Ratas Sprague-Dawley , Receptores AMPA/metabolismo , Esquizofrenia/inducido químicamente , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatología , Conducta Social , Sinaptofisina/metabolismoRESUMEN
Tonic immobility (TI) is an innate defensive response exhibited by prey when physical contact with a predator is prolonged and inescapable. This defensive response is able to activate analgesia mechanisms; this activation has adaptive value because, during an attack by a predator, the manifestation of recuperative behaviors can affect the appropriate behavioral defense strategy. Some studies have suggested that similar structures of the central nervous system can regulate the response of both TI and nociception. Thus, this study evaluated the effect of chemical lesion through the administration of ibotenic acid in restricted brain areas of the periaqueductal gray matter (PAG) in guinea pig on the TI response and nociception evaluated in the hot plate test before and after emission of TI. The data showed that an irreversible chemical lesion in the ventrolateral PAG reduced of the TI response as well as defensive antinociception. However, a lesion in the dorsal PAG blocked the defensive antinociception induced by TI but did not alter TI duration. In summary, one could hypothesize that the neural substrates responsible for defensive behavior and antinociception represent similar systems that are distinct in modulation. Thus, the ventrolateral PAG has been associated with the modulation of TI and the defensive antinociception induced by TI. In contrast, the integrity of the dorsal PAG should be necessary for defensive antinociception to occur but not to elicit TI behavior in guinea pigs.
Asunto(s)
Analgesia , Ácido Iboténico/farmacología , Pérdida de Tono Postural/fisiología , Sustancia Gris Periacueductal/fisiopatología , Animales , Cobayas , Ácido Iboténico/administración & dosificación , Masculino , Microinyecciones , Dimensión del Dolor , Sustancia Gris Periacueductal/efectos de los fármacosRESUMEN
Generalised tonic-clonic seizures, generated by abnormal neuronal hyper-activity, cause a significant and long-lasting increase in the nociceptive threshold. The pedunculopontine tegmental nucleus (PPTN) plays a crucial role in the regulation of seizures as well as the modulation of pain, but its role in postictal antinociceptive processes remains unclear. In the present study, we aimed to investigate the involvement of PPTN neurons in the postictal antinociception. Wistar rats had their tail-flick baseline recorded and were injected with ibotenic acid (1.0⯵g/0.2⯵L) into the PPTN, aiming to promote a local neurotoxic lesion. Five days after the neuronal damage, pentylenetetrazole (PTZ; 64â¯mg/kg) was intraperitoneally administered to induce tonic-clonic seizures. The tail-withdrawal latency was measured immediately after the seizures (0â¯min) and subsequently at 10-min intervals until 130â¯min after the seizures were induced pharmacologically. Ibotenic acid microinjected into the PPTN did not reduce the PTZ-induced seizure duration and severity, but it diminished the postictal antinociception from 0 to 130â¯min after the end of the PTZ-induced tonic-clonic seizures. These results suggest that the postictal antinociception depends on the PPTN neuronal cells integrity.
Asunto(s)
Analgesia , Ácido Iboténico/toxicidad , Núcleo Tegmental Pedunculopontino/fisiología , Convulsiones/fisiopatología , Animales , Ácido Iboténico/administración & dosificación , Masculino , Microinyecciones , Dimensión del Dolor , Pentilenotetrazol/farmacología , Ratas , Convulsiones/inducido químicamente , Factores de TiempoRESUMEN
It has been shown that electrical stimulation of the mesencephalic tectum (MT) provokes defensive responses in both humans and rodents. During an emotional aversive state, some convergent studies have also demonstrated the existence of a complex interaction between endogenous opioid peptide- and γ-aminobutyric acid (GABA)-containing connections during fear-induced responses. It has been proposed that opioid neurons exert an influence on GABAergic interneurons, which, in turn, exert inhibitory tonic control on the mesencephalic excitatory pathways. Thus, opioid peptides can disinhibit neurons that are tonically inhibited by GABA, therefore, modulating the expression of defensive behavioural reactions. In the present work, we used both electric stimulation and microinjections of the GABAA receptor antagonist bicuculline in the inferior colliculus (IC) of Wistar rats in combination with microinjections of µ- and κ-opioid receptor selective agonists into the dorsal columns of periaqueductal grey matter (dPAG) to evaluate the effects on panic-like behaviours elicited by IC electrical and chemical stimulation. The present results showed that neurochemical lesions of the dPAG caused a significant impairment in the organisation of defensive responses by IC neurons, reducing the duration [t(14)=3.0; p<0.01] of defensive immobility and the duration [t(14)=2.8; p<0.05] and frequency [t(14)=2.5; p<0.05] of escape. Paradoxically, treating the dPAG with the µ-opioid receptor agonist met-enkephalin caused a significant reduction of panic-like behaviours induced by both electrical and chemical stimulation of the IC, increasing the escape behaviour threshold [F(2,23)=13.5; p<0.001] and decreasing the frequency [F(3,36)=11.7; p<0.001] and duration [F(3,36)=11.6; p<0.001] of escape and the duration of defensive immobility [F(3,36)=16.1; p<0.05]. In contrast, treating the dPAG with the κ-opioid receptor agonist salvinorin-A increased the frequency [F(3,36)=12.4; p<0.01] and duration [F(3,34)=16.1; p<0.01] of defensive immobility induced by GABAA receptor blockade in the IC. The present results suggest the existence of a complex neuronal network in the MT in which endogenous opioid peptides and GABAergic pathways interact in the control of fear-related behavioural responses.
Asunto(s)
Analgésicos Opioides/farmacología , Colículos Inferiores/fisiología , Pánico/fisiología , Sustancia Gris Periacueductal/fisiología , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/metabolismo , Animales , Bicuculina/farmacología , Diterpenos de Tipo Clerodano/farmacología , Estimulación Eléctrica , Encefalina Metionina/farmacología , Reacción de Fuga/fisiología , Reacción Cataléptica de Congelación/fisiología , Antagonistas de Receptores de GABA-A/farmacología , Ácido Iboténico , Colículos Inferiores/efectos de los fármacos , Masculino , Neuronas/efectos de los fármacos , Neuronas/fisiología , Sustancia Gris Periacueductal/efectos de los fármacos , Ratas Wistar , Receptores de GABA-A/metabolismo , Receptores Opioides kappa/agonistas , Receptores Opioides mu/agonistasRESUMEN
AIM: Although periaqueductal grey matter activation is known to elicit respiratory and cardiovascular responses, the role of this midbrain area in the compensatory responses to hypoxia is still unknown. To test the participation of the periaqueductal grey matter in cardiorespiratory and thermal responses to hypoxia in adult male Wistar rats, we performed a chemical lesion of the dorsolateral/dorsomedial or the ventrolateral/lateral periaqueductal grey matter using ibotenic acid. METHODS: Pulmonary ventilation, mean arterial pressure, heart rate and body temperature were measured in unanaesthetized rats during normoxic and hypoxic exposure (5, 15, 30 min, 7% O2). RESULTS: An ibotenic acid lesion of the dorsolateral/dorsomedial periaqueductal grey matter caused a higher increase in pulmonary ventilation (67.1%, 1730±282.5 mL kg(-1) min(-1)) compared to the Sham group (991.4±194 mL kg(-1) min(-1)) after 15 min in hypoxia, whereas for the ventrolateral/Lateral periaqueductal grey matter lesion, no differences were observed between groups. Mean arterial pressure, heart rate and body temperature were not affected by a dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter lesion. CONCLUSION: Middle to caudal portions of the dorsolateral/dorsomedial periaqueductal grey matter neurones modulate the hypoxic ventilatory response, exerting an inhibitory modulation during low O2 situations. In addition, the middle to caudal portions of the dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter do not appear to exert a tonic role on cardiovascular or thermal parameters during normoxic and hypoxic conditions.
Asunto(s)
Hipoxia/fisiopatología , Pulmón/inervación , Sustancia Gris Periacueductal/fisiopatología , Ventilación Pulmonar , Animales , Presión Arterial , Regulación de la Temperatura Corporal , Dióxido de Carbono/sangre , Estado de Conciencia , Modelos Animales de Enfermedad , Frecuencia Cardíaca , Hipoxia/sangre , Ácido Iboténico/toxicidad , Masculino , Oxígeno/sangre , Sustancia Gris Periacueductal/efectos de los fármacos , Sustancia Gris Periacueductal/patología , Ventilación Pulmonar/efectos de los fármacos , Ratas Wistar , Reflejo , Factores de TiempoRESUMEN
The medullary raphé is an important component of the central respiratory network, playing a key role in CO2 central chemoreception. However, its participation in hypoxic ventilatory responses is less understood. In the present study, we assessed the role of nucleus raphé obscurus (ROb), and specifically 5-HT neurons confined in the ROb, on ventilatory and thermoregulatory responses to hypoxia. Chemical lesions of the ROb were performed using either ibotenic acid (non-specific lesion; control animals received PBS) or anti-SERT-SAP (5-HT specific lesion; control animals received IgG-SAP). Ventilation (VËE; whole body plethysmograph) and body temperature (Tb; data loggers) were measured during normoxia (21% O2, N2 balance) and hypoxia exposure (7% O2, N2 balance, 1h) in conscious adult rats. Ibotenic acid or anti-SERT-SAP-induced lesions did not affect baseline values of VËE and Tb. Similarly, both lesion procedures did not alter the ventilatory or thermoregulatory responses to hypoxia. Although evidence in the literature suggests a role of the rostral medullary raphé in hypoxic ventilatory responses, under the present experimental conditions our data indicate that caudal medullary raphé (ROb) and its 5-HT neurons neither participate in the tonic maintenance of breathing nor in the ventilatory and thermal responses to hypoxia.
Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Hipoxia/patología , Hipoxia/fisiopatología , Ventilación Pulmonar/fisiología , Núcleos del Rafe/patología , Neuronas Serotoninérgicas/fisiología , Animales , Anticuerpos/farmacología , Análisis de los Gases de la Sangre , Temperatura Corporal/efectos de los fármacos , Temperatura Corporal/fisiología , Regulación de la Temperatura Corporal/efectos de los fármacos , Recuento de Células , Modelos Animales de Enfermedad , Agonistas de Aminoácidos Excitadores/toxicidad , Ácido Iboténico/toxicidad , Masculino , Microinyecciones , Pletismografía Total , Ventilación Pulmonar/efectos de los fármacos , Proteínas de Unión al ARN/inmunología , Ratas , Ratas Wistar , Serotonina/metabolismo , Factores de TiempoRESUMEN
The periaqueductal gray (PAG) is a midbrain structure directly involved in the modulation of defensive behaviors. It has direct projections to several central nuclei that are involved in cardiorespiratory control. Although PAG stimulation is known to elicit respiratory responses, the role of the PAG in the CO(2)-drive to breathe is still unknown. The present study assessed the effect of chemical lesion of the dorsolateral and dorsomedial and ventrolateral/lateral PAG (dlPAG, dmPAG, and vPAG, respectively) on cardiorespiratory and thermal responses to hypercapnia. Ibotenic acid (IBO) or vehicle (PBS, Sham group) was injected into the dlPAG, dmPAG, or vPAG of male Wistar rats. Rats with lesions outside the dlPAG, dmPAG, or vPAG were considered as negative controls (NC). Pulmonary ventilation (VE: ), mean arterial pressure (MAP), heart rate (HR), and body temperature (Tb) were measured in unanesthetized rats during normocapnia and hypercapnic exposure (5, 15, 30 min, 7 % CO(2)). IBO lesioning of the dlPAG/dmPAG caused 31 % and 26.5 % reductions of the respiratory response to CO(2) (1,094.3 ± 115 mL/kg/min) compared with Sham (1,589.5 ± 88.1 mL/kg/min) and NC groups (1,488.2 ± 47.7 mL/kg/min), respectively. IBO lesioning of the vPAG caused 26.6 % and 21 % reductions of CO(2) hyperpnea (1,215.3 ± 108.6 mL/kg/min) compared with Sham (1,657.3 ± 173.9 mL/kg/min) and NC groups (1,537.6 ± 59.3). Basal VE: , MAP, HR, and Tb were not affected by dlPAG, dmPAG, or vPAG lesioning. The results suggest that dlPAG, dmPAG, and vPAG modulate hypercapnic ventilatory responses in rats but do not affect MAP, HR, or Tb regulation in resting conditions or during hypercapnia.
Asunto(s)
Hipercapnia/fisiopatología , Sustancia Gris Periacueductal/fisiología , Ventilación Pulmonar/efectos de los fármacos , Animales , Análisis de los Gases de la Sangre , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Temperatura Corporal/efectos de los fármacos , Temperatura Corporal/fisiología , Dióxido de Carbono/sangre , Dióxido de Carbono/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Ácido Iboténico/toxicidad , Masculino , Sustancia Gris Periacueductal/anatomía & histología , Sustancia Gris Periacueductal/efectos de los fármacos , Ventilación Pulmonar/fisiología , Ratas , Ratas Wistar , VivisecciónRESUMEN
Rats with a neonatal ventral hippocampal lesion (NVHL) have been used to model certain features of schizophrenia because they display dopaminergic activity and behavioral alterations consistent with a dysfunctional prefrontal cortex after puberty. Microdialysis studies in normal rats demonstrated increased prefrontal dopamine release during the incentive phase of behavior in an experimental situation specifically designed to evidence this behavioral aspect: the so called "sensory-specific satiety" procedure. Our hypothesis is that if dopaminergic activity in the prefrontal cortex of NVHL rats differs from sham lesioned rats, the responsiveness to the aforementioned experimental situation should also be different. Extracellular medial prefrontal dopamine outflow increased in hungry control rats when they had access to food and decreased across satiety. It increased again when a new food was presented, even when the rats were satiated. NVHL rats also had increased dopamine prefrontal outflow in these conditions, but it remained high after the end of the consumption period. The food consumption behavior declined less rapidly and the reinstatement of food consumption, usually produced by new food, did not occur in NVHL rats, provided the lesions were large. These data were discussed in relation to several theoretical backgrounds developed about the incentive aspect of behavior and for understanding the pathophysiology of schizophrenia.
Asunto(s)
Dopamina/metabolismo , Hipocampo/fisiopatología , Corteza Prefrontal/metabolismo , Respuesta de Saciedad/fisiología , Animales , Animales Recién Nacidos , Ingestión de Alimentos/fisiología , Hipocampo/efectos de los fármacos , Ácido Iboténico/toxicidad , Microdiálisis , Corteza Prefrontal/fisiopatología , Ratas , Ratas Sprague-DawleyRESUMEN
The ability to react fast and efficiently in threatening situations is paramount for the survival of organisms and has been decisive in our evolutionary history. Defense mechanisms in primates rely on the fast recognition of potential predators and facial expressions of conspecifics. The neural circuitry responsible for the detection of threat is generally thought to be centered on the amygdala. Although it is a pivotal structure in the processing of emotional stimuli, the amygdala does not seem necessary for the early stages of this process. Here we show that bilateral neurotoxic lesions of the superior colliculus in infant capuchins monkeys impaired the recognition of a rubber-snake in a threat-reward conflict task. Lesioned monkeys were uninhibited by a snake in a food-reward retrieval task. Lack of inhibition in the task was observed over the course of 15 weeks. The long lasting recognition impairment of a natural predator observed here is similar to the tameness aspects of Kluver-Bucy syndrome, indicating an important role of this structure in threat recognition.
Asunto(s)
Conflicto Psicológico , Reacción de Fuga/fisiología , Conducta Alimentaria/fisiología , Inhibición Psicológica , Recompensa , Colículos Superiores/fisiopatología , Animales , Cebus , Modelos Animales de Enfermedad , Reacción de Fuga/efectos de los fármacos , Miedo/fisiología , Humanos , Ácido Iboténico/administración & dosificación , Ácido Iboténico/toxicidad , Instilación de Medicamentos , Síndrome de Kluver-Bucy , Neurotoxinas/administración & dosificación , Neurotoxinas/toxicidad , Reconocimiento Visual de Modelos , Tiempo de Reacción/fisiología , Serpientes , Colículos Superiores/efectos de los fármacos , Colículos Superiores/crecimiento & desarrolloRESUMEN
In spite of over 30 years of research, the role of the Insular Cortex (IC) in taste memory still remains elusive. To study the role of the IC in taste memory, we used conditioned taste aversion (CTA) for two different concentrations of saccharin; 0.1% which is highly preferred, and 0.5% which is non-preferred. Rats that had been IC lesioned bilaterally with ibotenic acid (15 mg/ml) before CTA showed significant learning impairments for saccharin 0.1% but not for saccharin 0.5%. To test CTA memory retention, rats lesioned a week after CTA training became completely amnesic for saccharin 0.1% yet only mildly impaired for saccharin 0.5%. Interestingly, the resulting preference for either concentration matched that of IC lesioned animals when exposed to either saccharin solution for the first time, but not those of sham animals, implying that IC lesions after CTA for either saccharin solution rendered complete amnesia, irrespective of the original preference. Our data indicate that an intact IC is essential for CTA learning and retention, as well as for an early neophobic response, but not for taste preference itself. Our data supports a model where the IC is involved in general taste rejection.
Asunto(s)
Corteza Cerebral/fisiología , Percepción del Gusto/fisiología , Gusto/fisiología , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiopatología , Condicionamiento Psicológico/fisiología , Ácido Iboténico/toxicidad , Masculino , Ratas , Ratas Wistar , Retención en Psicología/fisiologíaRESUMEN
In fear-associated learning paradigms, hippocampal lesions induce memory deficits of recent but not remote memories, while amygdala lesions produce retention deficits irrespective of the age of the memory. In conditioned taste aversion (CTA), non-hippocampal mediated learning paradigm, the insular vortex (IC) has shown to have a crucial role in consolidation and storage of CTA memory. Due to the functional and anatomical similarities to the hippocampus, a time dependent role of the IC in CTA retention cannot be ruled out. To test whether the IC shows a time dependent role in CTA memory retention, male Wistar rats were CTA trained on saccharin 0.1% (LiCl 0.15M, 2% b/w, 40 min after drinking) and lesioned with ibotenic acid (200-300 nL, 5mg/mL) unilaterally into the IC 1 week or bilaterally 1 or 6 weeks after CTA. CTA memory was completely disrupted in both bilateral lesion groups but unaffected in the unilateral lesioned group. The resulting preference was comparable to that of the bilaterally IC lesioned animals exposed to the taste for the first time, proving that in these animals a complete amnesic state was achieved. Bilaterally IC lesioned rats showed normal discrimination between preferred (sucrose 5%) and non-preferred (quinone) tastes. Our data indicates that the involvement of the IC in CTA is not time dependent and that CTA memories are stored in each hemisphere separately.
Asunto(s)
Reacción de Prevención/fisiología , Corteza Cerebral/fisiología , Condicionamiento Psicológico/fisiología , Retención en Psicología/fisiología , Gusto/fisiología , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Condicionamiento Psicológico/efectos de los fármacos , Ácido Iboténico/farmacología , Masculino , Microinyecciones , Ratas , Ratas Wistar , Retención en Psicología/efectos de los fármacos , Estadísticas no Paramétricas , Gusto/efectos de los fármacos , Factores de TiempoRESUMEN
The pedunculopontine tegmental nucleus (PPTg) targets nuclei in the basal ganglia, including the substantia nigra pars compacta (SNc), in which neuronal loss occurs in Parkinson's disease, a condition in which patients show cognitive as well as motor disturbances. Partial loss and functional abnormalities of neurons in the PPTg are also associated with Parkinson's disease. We hypothesized that the interaction of PPTg and SNc might be important for cognitive impairments and so investigated whether disrupting the connections between the PPTg and SNc impaired learning of a conditioned avoidance response (CAR) by male Wistar rats. The following groups were tested: PPTg unilateral; SNc unilateral; PPTg-SNc ipsilateral (ipsilateral lesions in PPTg and SNc); PPTg-SNc contralateral (contralateral lesions in PPTg and SNc); sham lesions (of each type). SNc lesions were made with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine HCl (MPTP, 0.6micromol); PPTg lesions with ibotenate (24nmol). After recovery, all rats underwent 50-trial sessions of 2-way active avoidance conditioning for 3 consecutive days. Rats with unilateral lesions in PPTg or SNc learnt this, however rats with contralateral (but not ipsilateral) combined lesions in both structures presented no sign of learning. This effect was not likely to be due to sensorimotor impairment because lesions did not affect reaction time to the tone or footshock during conditioning. However, an increased number of non-responses were observed in the rats with contralateral lesions. The results support the hypothesis that a functional interaction between PPTg and SNc is needed for CAR learning and performance.
Asunto(s)
Reacción de Prevención/fisiología , Condicionamiento Clásico/fisiología , Vías Nerviosas/citología , Núcleo Tegmental Pedunculopontino/citología , Sustancia Negra/citología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Análisis de Varianza , Animales , Dopamina/metabolismo , Lateralidad Funcional/fisiología , Ácido Iboténico/farmacología , Masculino , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/metabolismo , Neurotoxinas/farmacología , Núcleo Tegmental Pedunculopontino/efectos de los fármacos , Núcleo Tegmental Pedunculopontino/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Tiempo de Reacción/fisiología , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismo , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiologíaRESUMEN
Rats with a bilateral neonatal ventral hippocampus lesion (NVHL) are used as models of neurobiological aspects of schizophrenia. In view of their decreased number of GABAergic interneurons, we hypothesized that they would show increased reactivity to acoustic stimuli. We systematically characterized the acoustic reactivity of NVHL rats and sham operated controls. They were behaviourally observed during a loud white noise. A first cohort of 7 months' old rats was studied. Then the observations were reproduced in a second cohort of the same age after characterizing the reactivity of the same rats to dopaminergic drugs. A third cohort of rats was studied at 2, 3, 4, 5 and 6 months. In subsets of lesioned and control rats, inferior colliculus auditory evoked potentials were recorded. A significant proportion of rats (50-62%) showed aberrant audiogenic responses with explosive wild running resembling the initial phase of audiogenic seizures. This was not correlated with their well-known enhanced reactivity to dopaminergic drugs. The proportion of rats showing this strong reaction increased with rats' age. After the cessation of the noise, NVHL rats showed a long freezing period that did neither depend on the size of the lesion nor on the rats' age. The initial negative deflection of the auditory evoked potential was enhanced in the inferior colliculus of only NVHL rats that displayed wild running. Complementary anatomical investigations using X-ray scans in the living animal, and alizarin red staining of brain slices, revealed a thin layer of calcium deposit close to the medial geniculate nuclei in post-NVHL rats, raising the possibility that this may contribute to the hyper-reactivity to sounds seen in these animals. The findings of this study provide complementary information with potential relevance for the hyper-reactivity noted in patients with schizophrenia, and therefore a tool to investigate the underlying biology of this endophenotype.
Asunto(s)
Vías Auditivas/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Hipocampo/fisiopatología , Actividad Motora/efectos de los fármacos , Reflejo de Sobresalto/efectos de los fármacos , Estimulación Acústica , Factores de Edad , Anfetamina/toxicidad , Análisis de Varianza , Animales , Vías Auditivas/fisiopatología , Cocaína/toxicidad , Electrodos Implantados , Electroencefalografía , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Hipocampo/efectos de los fármacos , Hipercinesia/inducido químicamente , Ácido Iboténico/toxicidad , Imagen por Resonancia Magnética , Masculino , Plasticidad Neuronal/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Coloración y EtiquetadoRESUMEN
INTRODUCTION: Usually, most commercial platforms that adapt to the stereotaxic apparatus in neonatal rats or small animals, to carry out surgery are very expensive. Moreover, the operator must have certain experience in its handling. DEVELOPMENT: The present work presents two platforms, one of them made in acrylic and the other of expanded polystyrene. These adapt perfectly to conventional stereotaxic apparatus, while operator does not require a great entrainment to carry out the surgical procedure. Histological slides of the prefrontal cortex, ventral hippocampus and basolateral amygdala from adult rats (postnatal day 70), staining with cresyl violet are shown. The neonatal lesions were made at postnatal day 7 with ibotenic acid applied in the prefrontal cortex, ventral hippocampus or basolateral amygdala. CONCLUSIONS: The present data suggest that it is possible to carry out lesions or to apply drugs in neonatal rats, by using an acrylic or expanded polystyrene adaptor for the stereotaxic apparatus. These have the advantage of being economic and having a simple design. Also, the type of anesthesia used in neonatal lesion rats, is discussed.
Asunto(s)
Encéfalo/cirugía , Técnicas Estereotáxicas , Animales , Animales Recién Nacidos , Conducta Animal , Encéfalo/anatomía & histología , Encéfalo/metabolismo , Encéfalo/patología , Agonistas de Aminoácidos Excitadores/toxicidad , Ácido Iboténico/toxicidad , Actividad Motora , Procedimientos Neuroquirúrgicos/instrumentación , Procedimientos Neuroquirúrgicos/métodos , Ratas , Ratas Sprague-Dawley , Coloración y Etiquetado , Técnicas Estereotáxicas/economía , Técnicas Estereotáxicas/instrumentaciónRESUMEN
Located in the lower brainstem, the paratrigeminal nucleus (Pa5) is related to cardiorespiratory autonomic reflex functions. To characterize the structures' role in blood pressure regulation and baroreflex response, both resting cardiovascular parameters and reflex responses were evaluated during phenylephrine-produced pressor responses in non-anaesthetized rats with or without bilateral chemical Pa5 ablation. The Pa5-ablated animals, in contrast to the Pa5-intact control animals, presented increased resting arterial pressure (115+/-4 vs. 100+/-3 mm Hg), decreased heart (293+/-10 vs. 315+/-7 bpm) and increase of the respiratory (104+/-3 vs. 94+/-5 rpm) rates, larger pressor responses and reduced baroreflex index (1.6+/-0.2 vs. 2.8+/-0.2, p<0.05). The cardiovascular changes, compatible to those produced by nucleus of the solitary tract (NTS) lesions in non-anaesthetized rats, indicate a reduction of both the sympathetic and cardiac components of the baroreflex response. Further analyses showed the Pa5 mediates reflex responses to smaller blood pressure increases, while the NTS would be predominantly active in surges over 40 mm Hg. Thus, the integrity of the Pa5 is important for resting blood pressure maintenance as for a full baroreceptor response.
Asunto(s)
Sistema Nervioso Autónomo/fisiología , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Fenómenos Fisiológicos Cardiovasculares , Bulbo Raquídeo/fisiología , Neuronas/fisiología , Anestésicos/farmacología , Animales , Sistema Nervioso Autónomo/anatomía & histología , Desnervación , Frecuencia Cardíaca/fisiología , Ácido Iboténico , Masculino , Bulbo Raquídeo/anatomía & histología , Neurotoxinas , Ratas , Ratas Wistar , Núcleo Solitario/fisiología , Sistema Nervioso Simpático/anatomía & histología , Sistema Nervioso Simpático/fisiología , Núcleo Espinal del Trigémino/anatomía & histologíaRESUMEN
The anteromedial extrastriate complex has been proposed to play an essential role in a spatial orientation system in rats. To gain more information about that possible role, in the present work, two questions were addressed: 1. Are allocentric visual cues relevant for acquisition of the orientation task in the Lashley III maze? 2. Is this integration of allocentric inputs in the anteromedial visual complex relevant in the retention of this test? While a control group of rats was trained keeping the maze in the same position, the experimental group was trained with the maze rotated counterclockwise by 144 degrees from session to session. Control rats reached learning criterion significantly earlier and with less errors than the experimental ones (p<.05). After 11 sessions, rats of both groups received stereotaxic injections of ibotenic acid in the anteromedial complex. In the retention test one week after surgery, the control group, which had been able to learn using egocentric and allocentric visual cues, showed a greater deficit than the experimental animals (p<.05). These results confirm the role of the anteromedial complex in the processing of visuospatial orientation tasks and demonstrate the integration of allocentric visual cues in the solution of those tasks.
Asunto(s)
Animales , Masculino , Ratas , Aprendizaje por Laberinto/fisiología , Orientación/fisiología , Retención en Psicología/fisiología , Corteza Visual/fisiología , Señales (Psicología) , Agonistas de Aminoácidos Excitadores/farmacología , Ácido Iboténico/farmacología , Corteza Visual/efectos de los fármacosRESUMEN
Lesion of the nucleus basalis magnocellularis (nbm) is a suitable approach to study cognitive deficit and behavior alterations involving cholinergic dysfunction, which is associated with the major types of dementia. Cortical astrogliosis also has been described in this model, but it is not clear whether hippocampal astrocytes are activated. In this study, we investigated possible specific astrocyte alterations in the hippocampi of Wistar rats submitted to nbm damage with ibotenic acid, investigating the content and immunohistochemistry of glial fibrillary acidic protein (GFAP), as well as S100B protein content, glutamate uptake and glutamine synthetase activity on the 7th and 28th post-lesion days. Cognitive deficit was confirmed by the step-down inhibitory avoidance task. Interestingly, we found a decrease in GFAP content, S100B content and glutamate uptake activity in the hippocampus on the 28th day after nbm lesion. No alterations were observed in glutamine synthetase activity or in the cerebrospinal fluid S100B content. Although our data suggest caution in the use of nbm lesion with ibotenic acid as a dementia model, it is possible that these alterations could contribute to the cognitive deficit observed in these rats.
Asunto(s)
Astrocitos/citología , Reacción de Prevención/fisiología , Núcleo Basal de Meynert/fisiología , Fibras Colinérgicas/metabolismo , Demencia/fisiopatología , Hipocampo/citología , Animales , Astrocitos/metabolismo , Núcleo Basal de Meynert/citología , Núcleo Basal de Meynert/efectos de los fármacos , Daño Encefálico Crónico/inducido químicamente , Recuento de Células , Demencia/metabolismo , Modelos Animales de Enfermedad , Conducta Exploratoria/fisiología , Estudios de Seguimiento , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Ácido Glutámico/metabolismo , Habituación Psicofisiológica/fisiología , Hipocampo/metabolismo , Ácido Iboténico , Inmunohistoquímica , Masculino , Factores de Crecimiento Nervioso/metabolismo , Ratas , Ratas Wistar , Subunidad beta de la Proteína de Unión al Calcio S100 , Proteínas S100/metabolismo , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
The anteromedial extrastriate complex has been proposed to play an essential role in a spatial orientation system in rats. To gain more information about that possible role, in the present work, two questions were addressed: 1. Are allocentric visual cues relevant for acquisition of the orientation task in the Lashley III maze? 2. Is this integration of allocentric inputs in the anteromedial visual complex relevant in the retention of this test? While a control group of rats was trained keeping the maze in the same position, the experimental group was trained with the maze rotated counterclockwise by 144 degrees from session to session. Control rats reached learning criterion significantly earlier and with less errors than the experimental ones (p<.05). After 11 sessions, rats of both groups received stereotaxic injections of ibotenic acid in the anteromedial complex. In the retention test one week after surgery, the control group, which had been able to learn using egocentric and allocentric visual cues, showed a greater deficit than the experimental animals (p<.05). These results confirm the role of the anteromedial complex in the processing of visuospatial orientation tasks and demonstrate the integration of allocentric visual cues in the solution of those tasks.
Asunto(s)
Aprendizaje por Laberinto/fisiología , Orientación/fisiología , Retención en Psicología/fisiología , Corteza Visual/fisiología , Animales , Señales (Psicología) , Agonistas de Aminoácidos Excitadores/farmacología , Ácido Iboténico/farmacología , Masculino , Ratas , Corteza Visual/efectos de los fármacosRESUMEN
There is evidence that serotonin [5-hydroxytryptamine (5-HT)] is involved in the physiological responses to hypercapnia. Serotonergic neurons represent the major cell type (comprising 15-20% of the neurons) in raphe magnus nucleus (RMg), which is a medullary raphe nucleus. In the present study, we tested the hypothesis 1) that RMg plays a role in the ventilatory and thermal responses to hypercapnia, and 2) that RMg serotonergic neurons are involved in these responses. To this end, we microinjected 1) ibotenic acid to promote nonspecific lesioning of neurons in the RMg, or 2) anti-SERT-SAP (an immunotoxin that utilizes a monoclonal antibody to the third extracellular domain of the serotonin reuptake transporter) to specifically kill the serotonergic neurons in the RMg. Hypercapnia caused hyperventilation and hypothermia in all groups. RMg nonspecific lesions elicited a significant reduction of the ventilatory response to hypercapnia due to lower tidal volume (Vt) and respiratory frequency. Rats submitted to specific killing of RMg serotonergic neurons showed no consistent difference in ventilation during air breathing but had a decreased ventilatory response to CO(2) due to lower Vt. The hypercapnia-induced hypothermia was not affected by specific or nonspecific lesions of RMg serotonergic neurons. These data suggest that RMg serotonergic neurons do not participate in the tonic maintenance of ventilation during air breathing but contribute to the ventilatory response to CO(2). Ultimately, this nucleus may not be involved in the thermal responses to CO(2).
Asunto(s)
Hipercapnia/metabolismo , Hiperventilación/etiología , Hipotermia/etiología , Neuronas/metabolismo , Ventilación Pulmonar , Núcleos del Rafe/metabolismo , Serotonina/metabolismo , Animales , Dióxido de Carbono , Modelos Animales de Enfermedad , Agonistas de Aminoácidos Excitadores/farmacología , Hipercapnia/inducido químicamente , Hipercapnia/complicaciones , Hipercapnia/fisiopatología , Hiperventilación/metabolismo , Hiperventilación/fisiopatología , Hipotermia/metabolismo , Hipotermia/fisiopatología , Ácido Iboténico/farmacología , Inmunotoxinas/farmacología , Masculino , Neuronas/efectos de los fármacos , Neuronas/patología , Núcleos del Rafe/efectos de los fármacos , Núcleos del Rafe/patología , Núcleos del Rafe/fisiopatología , Ratas , Ratas Wistar , Mecánica Respiratoria , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Volumen de Ventilación Pulmonar , Factores de TiempoRESUMEN
We determined if the dorsal raphe nucleus (DRN) exerts tonic control of basal and stimulated sodium and water intake. Male Wistar rats weighing 300-350 g were microinjected with phosphate buffer (PB-DRN, N = 11) or 1 microg/0.2 microl, in a single dose, ibotenic acid (IBO-DRN, N = 9 to 10) through a guide cannula into the DRN and were observed for 21 days in order to measure basal sodium appetite and water intake and in the following situations: furosemide-induced sodium depletion (20 mg/kg, sc, 24 h before the experiment) and a low dose of dietary captopril (1 mg/g chow). From the 6th day after ibotenic acid injection IBO-DRN rats showed an increase in sodium appetite (12.0 +/- 2.3 to 22.3 +/- 4.6 ml 0.3 M NaCl intake) whereas PB-DRN did not exceed 2 ml (P < 0.001). Water intake was comparable in both groups. In addition to a higher dipsogenic response, sodium-depleted IBO-DRN animals displayed an increase of 0.3 M NaCl intake compared to PB-DRN (37.4 +/- 3.8 vs 21.6 +/- 3.9 ml 300 min after fluid offer, P < 0.001). Captopril added to chow caused an increase of 0.3 M NaCl intake during the first 2 days (IBO-DRN, 33.8 +/- 4.3 and 32.5 +/- 3.4 ml on day 1 and day 2, respectively, vs 20.2 +/- 2.8 ml on day 0, P < 0.001). These data support the view that DRN, probably via ascending serotonergic system, tonically modulates sodium appetite under basal and sodium depletion conditions and/or after an increase in peripheral or brain angiotensin II.