Effects of chemical stimulation of the lateral wings of the dorsal raphe nucleus on panic-like defensive behaviors and Fos protein expression in rats

摘要

The lateral wings subnucleus of the dorsal raphe nucleus (1wDR) has been implicated in the modulation of panic-like behaviors, such as escape. Infusion of non- excitotoxic doses of the excitatory amino acid kainic acid into this subnucleus promptly evokes a vigorous escape response. In addition, rats exposed to panic-inducing situations show an increase in Fos protein expression in neurons within the 1wDR. In the present study, we first investigated whether key structures associated with the mediation of escape behavior are recruited after chemical stimulation of the 1wDR with kainic acid. We next investigated whether the infusion of the GABA(A) receptor antagonist bicuculline into the IwDR also evoked escape responses measured both in a circular arena and in the rat elevated T-maze. The effects of bicuculline in the circular arena were compared to those caused by the infusion of this antagonist into the ventrolateral periaqueductal gray (v1PAG), an area in close vicinity to the IwDR. The results showed that kainic acid infusion into the 1wDR increased Fos protein immunostaining in brain structures deeply involved in panic-like defensive behaviors, such as the periaqueductal gray and hypothalamus, but not the amygdala. As observed with kainic acid, bicuculline evoked a pronounced escape response in the circular arena when microinjected in the 1wDR, but not in the v1PAG. The escape-promoting effect of bicuculline in the 1wDR was also evidenced in the elevated T-maze. These findings strength the view that dysfunction in mechanisms controlling escape in the IwDR is critically implicated in the pathophysiology of panic disorder. (C) 2017 Elsevier B.V. All rights reserved.