PACAP in the BNST Produces Anorexia and Weight Loss in Male and Female Rats

Abstract

Recent gene association studies have implicated pituitary adenylate cyclase-activating peptide (PACAP) systems in several psychiatric disorders associated with stressor exposure, and we have argued that many of the behavioral consequences of repeated stressor exposure may depend on the expression of PACAP in the bed nucleus of the stria terminalis (BNST). One behavioral consequence of the activation of stress systems can be anorexia and subsequent weight loss, and both the activation of central PACAP systems as well as neuronal activity in the BNST have also been associated with anorexic states in rodents. Hence, we investigated the regulation of food and water intake and weight loss following BNST PACAP infusion. BNST PACAP38 dose-dependently decreased body weight, as well as food and water intake in the first 24 h following infusion. Because different BNST subregions differentially regulate stress responding, we further examined the effects of PACAP38 in either the anterior or posterior BNST. Anterior BNST PACAP38 infusion did not alter weight gain, whereas posterior PACAP38 infusion resulted in weight loss. PACAP38 infused into the lateral ventricles did not alter weight, suggesting that the effects of BNST-infused PACAP were not mediated by leakage into the ventricular system. These data suggest that PACAP receptor activation in posterior BNST subregions can produce anorexia and weight loss, and corroborate growing data implicating central PACAP activation in mediating the consequences of stressor exposure.

Pituitary Adenylate Cyclase-Activating Peptide in the Central Amygdala Causes Anorexia and Body Weight Loss via the Melanocortin and the TrkB Systems

“…Importantly, the lack of effect on motor activity attests that the reduction in food intake and the body weight loss induced by PACAP were not due to a general behavioral suppression, as already shown after administration of PACAP intracerebroventricularly as well as site-specifically in other brain areas (Kocho-Schellenberg et al, 2014;Mounien et al, 2009;Resch et al, 2011). Alternative explanations for the anorectic effect of intra-CeA PACAP should, however, be Anorectic effects of CeA PACAP A Iemolo et al considered.…”

“…PACAP doses were chosen based on those used by us and others in i.c.v. studies, as well as in intra-BNST and intrahypothalamus (Dore et al, 2013;Kocho-Schellenberg et al, 2014;Mounien et al, 2009;Resch et al, 2011); the dose of SHU 9119 were chosen based on previous studies (Blouet et al, 2009;Cheng et al, 2011;Mounien et al, 2009); the doses of k252a and D-Phe-CRF(12-41) were selected based on pilot experiments and previous studies (Erb and Stewart, 1999;Funk et al, 2006;Ou and Gean, 2006;Ou et al, 2010). PACAP and antagonists were administered as a cocktail in a single injection and at a volume of 0.5 μl per side.…”

PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin

“…Previous studies showed that a single 1-g dose of PACAP, injected centrally into the VMN before the nocturnal phase of feeding, produced a significant body weight loss 24 h postinjection (18). Similarly, when PACAP was administered centrally in the posterior region of the stria terminalis bed nucleus, weight loss was observed for 24 h postinjection in a dose-dependent manner (24). Recently, PACAP and thyrotropin-releasing hormone (TRH) were shown to be crucial in the ARC to the excitatory drive of the agoutirelated peptide-expressing neurons that control hunger (27).…”

Parabrachial nucleus (PBn) pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the amygdala: Implication for the sensory and behavioral effects of pain

“…For treatments, the rats were similarly restrained in a towel and PACAP or vehicle ( 0.05% BSA in saline ) was slowly infused (1 :g/0.5 :l each side) at 0.25 :l/min (Harvard Apparatus, Holliston, MA) through an internal cannula that projected 1 mm from the guide cannulae; the PAC1 receptor specific agonist maxadilan (from Ethan Lerner, Harvard/Massachusetts General Hospital) was similarly infused in some studies. The peptide concentrations and treatment procedures were similar to those described in previous work (Hammack et al, 2009; Koch-Schellenberg et al, 2014; Roman et al, 2014). The infusion cannula were left in place for an additional minute before removal.…”

“…The infusion cannula were left in place for an additional minute before removal. Animal body weights were determined before and 24 h after infusions for all experiments (Kocho-Schellenberg et al, 2014). At the end of each study, the rats were perfused with 4% paraformaldehyde and the brains cryosectioned for cresyl violet staining to confirm cannulae placement.…”