RESUMO
The dorsal premammillary nucleus (PMd) is a hypothalamic structure that plays a pivotal role in the processing of predatory threats. Lesions of this nucleus virtually eliminate the expression of defensive responses to predator exposure. However, little is known about the neurotransmitters responsible for these behavioral responses. Since PMd neurons express ionotropic glutamate receptors and exposure to predators have been shown to activate nitric oxide (NO) producing cells in this region, the aim of this study was to verify the involvement of glutamate and NO-mediated neurotransmission in defensive reactions modulated by the PMd. We tested in male Wistar rats the hypothesis that intra-PMd injection of the NMDA receptor antagonist, AP7, or the NO synthase inhibitor, N-propyl-L-arginine (NP), would attenuate behavioral responses induced by cat exposure. Our results showed that both AP7 and NP significantly attenuated the behavioral responses induced by the live cat. These results suggest that the NMDA/NO pathway plays an important role in the behavioral responses mediated by the PMd.
Assuntos
Mecanismos de Defesa , Medo , Corpos Mamilares/fisiologia , N-Metilaspartato/metabolismo , Óxido Nítrico/metabolismo , 2-Amino-5-fosfonovalerato/análogos & derivados , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Arginina/farmacologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Gatos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Medo/efeitos dos fármacos , Reação de Congelamento Cataléptica/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Corpos Mamilares/efeitos dos fármacos , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
In the present work, we sought to mimic the internal state changes in response to a predator threat by pharmacologically stimulating the brain circuit involved in mediating predator fear responses, and explored whether this stimulation would be a valuable unconditioned stimulus (US) in an olfactory fear conditioning paradigm (OFC). The dorsal premammillary nucleus (PMd) is a key brain structure in the neural processing of anti-predatory defensive behavior and has also been shown to mediate the acquisition and expression of anti-predatory contextual conditioning fear responses. Rats were conditioned by pairing the US, which was an intra-PMd microinjection of isoproterenol (ISO; ß-adrenoceptor agonist), with amyl acetate odor-the conditioned stimulus (CS). ISO (10 and 40 nmol) induced the acquisition of the OFC and the second-order association by activation of ß-1 receptors in the PMd. Furthermore, similar to what had been found for contextual conditioning to a predator threat, atenolol (ß-1 receptor antagonist) in the PMd also impaired the acquisition and expression of OFC promoted by ISO. Considering the strong glutamatergic projections from the PMd to the dorsal periaqueductal gray (dPAG), we tested how the glutamatergic blockade of the dPAG would interfere with the OFC induced by ISO. Accordingly, microinjections of NMDA receptor antagonist (AP5, 6 nmol) into the dPAG were able to block both the acquisition, and partially, the expression of the OFC. In conclusion, we have found that PMd ß-1 adrenergic stimulation is a good model to mimic predatory threat-induced internal state changes, and works as a US able to mobilize the same systems involved in the acquisition and expression of predator-related contextual conditioning.