RESUMO
The posterodorsal medial amygdala (MePD) has a high concentration of receptors for gonadal hormones, is a sexually dimorphic region and dynamically controls the reproductive behavior of both males and females. Neurotrophic factors can promote dendritic spine remodeling and change synaptic input strength in a region-specific manner. Here, we analyzed the gene and protein expression of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-1), polysialylated neural cell adhesion molecule (PSA-NCAM) and Ephrin-A4 in the MePD of adult males and females in diestrus, proestrus and estrus using real-time qPCR and fluorescent immunohistochemistry. The first approach showed their amplification except for Igf1 and the latter revealed that BDNF, IGF-1, PSA-NCAM and Ephrin-A4 are expressed in the MePD of the adult rats. Protein expression of these neurotrophic factors showed no differences between groups. However, proestrus females displayed a higher number of labelled puncta than males for BDNF expression and diestrus females for IGF-1 expression. In conjunction, results indicate that IGF-1 might be released rather than synthetized in the MePD, and the expression of specific neurotrophic factors varies specifically during proestrus. The dynamic modulation of BDNF and IGF-1 during this cyclic phase is coincident with synaptic changes and spine density remodeling in the MePD, the disinhibition of gonadotrophin secretion for ovulation and the display of sexual behavior.
Assuntos
Complexo Nuclear Corticomedial/fisiologia , Ciclo Estral , Fatores de Crescimento Neural/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Efrina-A4/análise , Efrina-A4/fisiologia , Feminino , Expressão Gênica , Masculino , Moléculas de Adesão de Célula Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Ratos Wistar , Caracteres SexuaisRESUMO
Tonic immobility (TI) is a temporary state of profound motor inhibition associated with great danger as the attack of a predator. Previous studies carried out in our laboratory evidenced high Fos-IR in the posteroventral region of the medial nucleus of the amygdala (MEA) after induction of the TI response. Here, we investigated the effects of GABAA and GABAB of the MEA on TI duration. Intra-MEA injections of the GABAA agonist muscimol and GABAB agonist baclofen reduced TI response, while intra-MEA injections of the GABAA antagonist bicuculline and GABAB antagonist phaclofen increased the TI response. Moreover, the effects observed with muscimol and baclofen administrations into MEA were blocked by pretreatment with bicuculline and phaclofen (at ineffective doses per se). Finally, the activation of GABAA and GABAB receptors in the MEA did not alter the spontaneous motor activity in the open field test. These data support the role of the GABAergic system of the MEA in the modulation of innate fear.
Assuntos
Complexo Nuclear Corticomedial/fisiologia , Agonistas de Receptores de GABA-A/fisiologia , Agonistas dos Receptores de GABA-B/fisiologia , Resposta de Imobilidade Tônica/fisiologia , Animais , Baclofeno/administração & dosagem , Baclofeno/análogos & derivados , Baclofeno/antagonistas & inibidores , Baclofeno/farmacologia , Bicuculina/administração & dosagem , Bicuculina/farmacologia , Complexo Nuclear Corticomedial/efeitos dos fármacos , Agonistas de Receptores de GABA-A/administração & dosagem , Agonistas de Receptores de GABA-A/farmacologia , Antagonistas de Receptores de GABA-A/administração & dosagem , Antagonistas de Receptores de GABA-A/farmacologia , Agonistas dos Receptores de GABA-B/administração & dosagem , Agonistas dos Receptores de GABA-B/farmacologia , Antagonistas de Receptores de GABA-B/administração & dosagem , Antagonistas de Receptores de GABA-B/farmacologia , Cobaias , Resposta de Imobilidade Tônica/efeitos dos fármacos , Masculino , Microinjeções , Atividade Motora/efeitos dos fármacos , Muscimol/administração & dosagem , Muscimol/antagonistas & inibidores , Muscimol/farmacologiaRESUMO
Oxytocin has central actions that modulate synaptic plasticity and the occurrence of social behavior in rodents. The posterodorsal medial amygdala (MePD) composes a sexually dimorphic neural circuit for the display of male sexual behavior. Local dendritic spines are notably plastic and affected by context-dependent social stimuli. Here, we examined the effects of the selective deletion of the OT gene (OTKO) in the number and shape of Golgi-impregnated dendritic spines in the MePD of näive and sexually experienced (SexExp) male mice (n=6 each group). Compared to the control wild-type mice (WT), OTKO näive mice did not differ in the density of dendritic spines, but there was a significant and more intense reduction in the number of spines in the WT/SexExp (â¼40%) than in the OTKO/SexExp (â¼25%). This structural change had a spine-specific feature. That is, sexual experience induced a decrease in the number of thin (â¼50%) and mushroom-like spines (â¼35%) at the same time that increased (â¼30%) the number of stubby/wide spines. In addition, the OTKO/SexExp animals have more thin and mushroom spines than the WT/SexExp ones (â¼25% and 55%, respectively; p <0.01 in all cases). In conjunction, these novel data indicate that OT participates in the spine remodeling, synaptic refinement, and social stimuli-dependent plasticity in the MePD of male mice.
Assuntos
Complexo Nuclear Corticomedial/fisiologia , Espinhas Dendríticas/fisiologia , Ocitocina/fisiologia , Comportamento Sexual , Animais , Complexo Nuclear Corticomedial/citologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ocitocina/genéticaRESUMO
The tonic immobility (TI) response is an innate fear behavior associated with intensely dangerous situations, exhibited by many species of invertebrate and vertebrate animals. In humans, it is possible that TI predicts the severity of posttraumatic stress disorder symptoms. This behavioral response is initiated and sustained by the stimulation of various groups of neurons distributed in the telencephalon, diencephalon and brainstem. Previous research has found the highest Fos-IR in the posteroventral part of the medial nucleus of the amygdala (MEA) during TI behavior; however, the neurotransmission of this amygdaloid region involved in the modulation of this innate fear behavior still needs to be clarified. Considering that a major drug class used for the treatment of psychopathology is based on serotonin (5-HT) neurotransmission, we investigated the effects of serotonergic receptor activation in the MEA on the duration of TI. The results indicate that the activation of the 5HT1A receptors or the blocking of the 5HT2 receptors of the MEA can promote a reduction in fear and/or anxiety, consequently decreasing TI duration in guinea pigs. In contrast, blocking the 5HT1A receptors or activating the 5HT2 receptors in this amygdalar region increased the TI duration, suggesting an increase in fear and/or anxiety. These alterations do not appear to be due to a modification of spontaneous motor activity, which might non-specifically affect TI duration. Thus, these results suggest a distinct role of the 5HT receptors in the MEA in innate fear modulation.
Assuntos
Complexo Nuclear Corticomedial/fisiologia , Medo/fisiologia , Resposta de Imobilidade Tônica , Receptor 5-HT1A de Serotonina/fisiologia , Receptor 5-HT2A de Serotonina/fisiologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/administração & dosagem , Animais , Ansiedade/fisiopatologia , Complexo Nuclear Corticomedial/efeitos dos fármacos , Medo/efeitos dos fármacos , Cobaias , Resposta de Imobilidade Tônica/efeitos dos fármacos , Ketanserina/administração & dosagem , Masculino , Agonistas do Receptor 5-HT1 de Serotonina/administração & dosagem , Antagonistas do Receptor 5-HT2 de Serotonina/administração & dosagemRESUMO
Previous results show that the activation of CRF type 1 (CRFR1) receptors of the medial amygdala (MeA) induces anxiogenic-like effects. The present study investigates the role played by medial amygdala CRF type 2 receptors (CRFR2) in the modulation of anxiety and panic-related responses. Male Wistar rats were administered into the MeA with the CRFR2 agonist urocortin 2 (0.5 e 1.0µg/0.2µl, experiment 1) or with the CRFR2 antagonist astressin 2-B (60ng/0.2µl, experiment 2) and 10min later tested in the elevated T-maze (ETM) for inhibitory avoidance and escape measurements. In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. In a third experiment, the effects of the combined treatment with urocortin 2 (1.0µg/0.2µl) and a sub-effective dose of astressin 2-B (30ng/0.2µl) were also investigated. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Results showed that urocortin 2, in the highest dose administered (1.0µg/0.2µl), facilitated ETM avoidance, an anxiogenic-like effect. Astressin 2-B, also in the highest dose (60ng/0.2µl), significantly decreased avoidance latencies, an anxiolytic-like effect. The lower dose of astressin 2-B (30ng/0.2µl) did not induce anxiolytic-like effects but was able to counteract the anxiogenic-like effects of urocortin 2. None of the compounds administered altered escape responses or locomotor activity measurements. These results suggest that CRFR2 in the medial amygdala, as CRFR1, selectively modulate an anxiety-related response.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Complexo Nuclear Corticomedial/fisiologia , Inibição Psicológica , Aprendizagem em Labirinto/fisiologia , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Análise de Variância , Animais , Ansiolíticos/farmacologia , Complexo Nuclear Corticomedial/efeitos dos fármacos , Hormônio Liberador da Corticotropina/farmacologia , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Microinjeções , Fragmentos de Peptídeos/farmacologia , Ratos , Tempo de Reação/efeitos dos fármacos , Receptores de Hormônio Liberador da Corticotropina/agonistas , Urocortinas/farmacologiaRESUMO
The medial amygdaloid nucleus (MeA) is involved in cardiovascular control. In the present study we report the effect of MeA pharmacological ablations caused by bilateral microinjections of the nonselective synaptic blocker CoCl2 on cardiac baroreflex responses in rats. MeA synaptic inhibition evoked by local bilateral microinjection of 100 nL of CoCl2 (1 mM) did not affect blood pressure or heart rate baseline, suggesting no tonic MeA influence on resting cardiovascular parameters. However, 10 min after CoCl2 microinjection into the MeA of male Wistar rats, the reflex bradycardic response evoked by intravenous infusion of phenylephrine was significantly enhanced when compared with the reflex bradycardic response observed before CoCl2. The treatment did not affect the tachycardic responses to the intravenous infusion of sodium nitroprusside (SNP). Baroreflex activity returned to control values 60 min after CoCl2 microinjections, confirming a reversible blockade. The present results indicate an involvement of the MeA in baroreflex modulation, suggesting that synapses in the MeA have an inhibitory influence on the bradycardic component of the baroreflex in conscious rats.