Panic-like defensive behavior but not fear-induced antinociception is differently organized by dorsomedial and posterior hypothalamic nuclei of Rattus norvegicus (Rodentia, Muridae)

J.A. Silva,A.F. Biagioni,N.C. Coimbra

doi:10.1590/s0100-879x2012007500037

Abstract

The hypothalamus is a forebrain structure critically involved in the organization of defensive responses to aversive stimuli. Gamma-aminobutyric acid (GABA)ergic dysfunction in dorsomedial and posterior hypothalamic nuclei is implicated in the origin of panic-like defensive behavior, as well as in pain modulation. The present study was conducted to test the difference between these two hypothalamic nuclei regarding defensive and antinociceptive mechanisms. Thus, the GABAA antagonist bicuculline (40 ng/0.2 µL) or saline (0.9% NaCl) was microinjected into the dorsomedial or posterior hypothalamus in independent groups. Innate fear-induced responses characterized by defensive attention, defensive immobility and elaborate escape behavior were evoked by hypothalamic blockade of GABAA receptors. Fear-induced defensive behavior organized by the posterior hypothalamus was more intense than that organized by dorsomedial hypothalamic nuclei. Escape behavior elicited by GABAA receptor blockade in both the dorsomedial and posterior hypothalamus was followed by an increase in nociceptive threshold. Interestingly, there was no difference in the intensity or in the duration of fear-induced antinociception shown by each hypothalamic division presently investigated. The present study showed that GABAergic dysfunction in nuclei of both the dorsomedial and posterior hypothalamus elicit panic attack-like defensive responses followed by fear-induced antinociception, although the innate fear-induced behavior originates differently in the posterior hypothalamus in comparison to the activity of medial hypothalamic subdivisions.

Highlights

The medial hypothalamus is thought to be part of a neurobiological substrate controlling defensive behavior [1,2]
It has been suggested that some hypothalamic nuclei such as the anterior hypothalamic nucleus, the dorsomedial division of the ventromedial nucleus and the dorsal premammillary nucleus are part of a circuit proposed as a medial hypothalamic zone (MHZ) defensive system, since there is an increase in Fos immunoreactivity in these structures during innate defensive responses elicited during predatory threatening [3]
Given the importance of the DMH and PH in antinociceptive processes associated with the defensive response or panic-like behavior, the aim of the present study was to investigate the characteristics of defensive responses elicited by GABAA receptor blockade in different divisions of the hypothalamus, including medial and posterior nuclei, and to determine if these reactions are followed by oscillation of the nociceptive threshold

Summary

Introduction

The medial hypothalamus is thought to be part of a neurobiological substrate controlling defensive behavior [1,2]. There is evidence that the MHZ defensive system is connected to other hypothalamic nuclei, including the lateral preoptic area, the dorsomedial rostral perifornical region, as well as the dorsomedial (DMH) and posterior (PH) hypothalamic nuclei [3] that justify more profound investigation of the specific role of these nuclei in panic attack-related behavior. Stimulation of the ventromedial hypothalamus [4] and PH [5] evokes panic attacks such as shortness of breath and increased arterial pressure and heart rate, the possibility of activation of both excitatory neurons and fibers of passage connecting these hypothalamic nuclei to other structures of the brain aversion system, such as the periaqueductal gray matter, cannot be ruled out.

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