Effects of reversible inactivation of the dorsomedial hypothalamus on panic- and anxiety-related responses in rats

Brazilian Journal of Medical and Biological Research

J.o.g. Nascimento²  H. Zangrossi Jr.¹  M.b. Viana¹ 

[1] ,Universidade Federal de São Paulo Departamento de Psiquiatria São Paulo SP ,Brasil

关键词: Muscimol;    Generalized anxiety disorder;    Panic disorder;    Dorsomedial hypothalamus;    Elevated T-maze;   

DOI  :  10.1590/S0100-879X2010007500075

来源: SciELO

【 摘 要 】

The medial hypothalamus is part of a neurobiological substrate controlling defensive behavior. It has been shown that a hypothalamic nucleus, the dorsomedial hypothalamus (DMH), is involved in the regulation of escape, a defensive behavior related to panic attacks. The role played by the DMH in the organization of conditioned fear responses, however, is less clear. In the present study, we investigated the effects of reversible inactivation of the DMH with the GABA A agonist muscimol on inhibitory avoidance acquisition and escape expression by male Wistar rats (approximately 280 g in weight) tested in the elevated T-maze (ETM). In the ETM, inhibitory avoidance, a conditioned defensive response, has been associated with generalized anxiety disorder. Results showed that intra-DMH administration of the GABA A receptor agonist muscimol inhibited escape performance, suggesting an antipanic-like effect (P < 0.05), without changing inhibitory avoidance acquisition. Although a higher dose of muscimol (1.0 nmol/0.2 µL; N = 7) also altered locomotor activity in an open field when compared to control animals (0.2 µL saline; N = 13) (P < 0.05), the lower dose (0.5 nmol/0.2 µL; N = 12) of muscimol did not cause any motor impairment. These data corroborate previous evidence suggesting that the DMH is specifically involved in the modulation of escape. Dysfunction of this regulatory mechanism may be relevant in the genesis/maintenance of panic disorder.

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