Print

Kocho-Schellenberg, Margaret

Psychology

2013

M.A.

The term "stress" has been used to describe any deviation of the body from homeostasis and exposure to stressors can elicit multiple responses. When stress becomes chronic, it can lead to detrimental effects including disease states such as anxiety disorders. The bed nucleus of the stria terminalis (BNST) has been argued to mediate many of the behavioral consequences of repeated/chronic stressor exposure, including anorexia, and subsequent effects on body weight. Pituitary adenylate cyclaseactivating peptide (PACAP), which is part of the vasoactive intestinal peptide (VIP) secretin-glucagon family, has both neurotransmitter and neurotrophic properties in the brain. When infused intracerebroventricularly or intraperitoneally, PACAP leads to weight loss and decreased food intake in several species, likely via action in brain regions related to stress responding. Moreover, when rats are repeatedly stressed for 7 days, elevated PACAP and PACI receptor mRNA is observed in the BNST oval nucleus, an area that has been implicated in mediating the effects of stress-induced anorexia. Hence, BNST PACAP activation may mimic some behavioral outcomes of repeated stressor exposure. In the current set of experiments we thus expected PACAP38 infusion into the BNST to result in anorexia and increased anxiety-like behavior, as is observed following repeated stressor exposure.
In the first experiment, we infused one of 4 doses (0 [mu]g, 0.1 [mu]g, 0.5 [mu]g or 1.0 [mu]g) of PACAP38 bilaterally into the BNST and examined weight change in the 24 hours post infusion. BNST PACAP38 dose-dependently decreased body weight, as well as food and water intake. Because different subregions of the BNST can have different effects on some forms of stress responding, we examined whether PACAP38 infused more discretely into either the anterior or posterior BNST produced different effects on weight change in the 24 hours post infusion. PACAP38 infused into the anterior BNST had no effect on weight change, while posterior PACAP38 infusion resulted in weight loss, as in experiment 1. Finally, we examined anterior versus posterior infusions of PACAP38 on anxiety-like behavior using the elevated plus maze (EPM). No effect of either anterior or posterior PACAP38 infusion was found on anxiety-like behavior using the EPM. However, PACAP38 infused into the anterior BNST produced significant weight loss in rats that were also tested on the EPM. These data suggest that anterior BNST PACAP may synergize with the stress produced by EPM exposure to reduce weight. Possible mechanisms underlying this synergy, including interactions with BNST corticotropin-releasing hormone (CRH) systems are discussed.