Serotonin 2C receptors within the basolateral amygdala induce acute fear-like responses in an open-field environment

Abstract Several studies indicate a role for the serotonin 2 subfamily (5-HT 2A , 5-HT 2B , 5-HT 2C ) in mediation of fear and anxiety responses. The current study began to examine the effects of stimulating 5-HT 2C receptors within the basolateral (BLA) or central nucleus of the amygdala (CeA) on acute fear-like responses in rats. Bilateral intra-BLA infusions of mCPP (3–3000 pmol), a mixed 5-HT 2 agonist, produced ultrasonic vocalization and reduced exploratory behavior while increasing the latency to investigate a novel object. These responses were attenuated by SB-242084, a 5-HT 2C -specific antagonist. Furthermore, a selective 5-HT 2C agonist, IL-639, produced a similar repertoire of behavioral effects with the exception of effects on time spent in the center of an open-field arena. Finally, infusions of mCPP into the CeA produced no anxiogenic behaviors suggesting that 5-HT 2C receptors primarily within the BLA are responsible for many of the acute fear-like responses reported here. To characterize further the neural circuits associated with 5-HT 2C -mediated fear responses, we assessed c- fos mRNA expression after intra-BLA infusions of mCPP, IL-639 or their vehicles. Whereas the overall regional pattern of c- fos mRNA induction for the two compounds was distinct, c- fos activation was confined primarily to limbic nuclei with the medial prefrontal cortex as a common regional target of each drug. These results suggest that activation of 5-HT 2C receptors within the BLA influences the activity of limbic circuits involved in the expression of acute innate fear responses.