Pituitary adenylate cyclase-activating polypeptide (PACAP)+ cells in the paraventricular nucleus of the thalamus: relationship with binge-type eating in male and female mice

Abstract

Rationale Both the paraventricular nucleus of the thalamus (PVT) and the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), are thought to be involved in food intake. Importantly, PACAP is expressed in cells of the PVT. Objectives To determine if PACAP in cells of the PVT might mediate some of the involvement of the PVT with palatable food intake. Methods In male and female C57BL/6 J mice and PACAP-Cre transgenic mice on a C57BL/6 J background, limited access to Milk Chocolate Ensure Plus® was used to establish a model of binge-type eating. Next, using quantitative real-time PCR, gene expression of PACAP in the PVT was measured in relation to this binge-type eating. Finally, using chemogenetics in PACAP-Cre transgenic mice, the effect of activation of PVT PACAP+ cells on binge-type eating was determined. Results Males and females both engaged in binge-type eating with Ensure, although females engaged in this behavior to a greater degree than males. While females also had a higher baseline level of PVT PACAP mRNA than males, only males showed an increase in levels of PACAP after a history of exposure to Ensure, and only males showed a reduction in levels of PACAP immediately prior to a binge session. Conversely, activation of PACAP+ cells in the PVT reduced binge-type eating of Ensure, specifically in male mice. Conclusions The present findings indicate that PVT PACAP+ cells influence and are influenced by binge-type eating. Thus, PACAP in the PVT might mediate some of the known involvement of the PVT with palatable food intake.