Stress-type specific changes of VIP signaling in limbic regions of the rat brain

Vasoactive intestinal peptide (VIP) is a highly abundant neuropeptide in the central nervous system, implicated in the regulation of numerous behavioral and physiological functions, including the central stress response. Notably, VIP and its cognate receptors, VPAC1 and VPAC2, are widely expressed in brain areas implicated in stress and anxiety regulation such as the amygdala. However, the exact role of VIP in stress function is not fully understood. The present study therefore examined how acute or chronic stress affect VIP and VPAC receptor gene expression in specific limbic brain regions of Sprague-Dawley rats using quantitative real-time PCR. Acute stress via forced swim exposure significantly increased VIP expression in the central amygdala (CeA) by 200 %, and in the medial amygdala (MeA) by 350 %. It also elevated VPAC1 receptor expression in the hypothalamic paraventricular nucleus (PVN), basolateral amygdala (BLA), and CeA, and VPAC2 receptor expression in the bed nucleus of the stria terminalis (BNST) and BLA. Chronic unpredictable stress induced both overlapping and distinct patterns, including upregulation of the VPAC1 receptor expression in the PVN by 120 % and the VPAC2 receptor in the CeA by 280 %, accompanied by slight downregulation of VIP in the CeA. These findings highlight a stress-duration-dependent and region-specific regulation of the VIP/VPAC receptor system and its potential role in modulating stress-related neural circuits.