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

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.