The purpose of the proposed studies is to determine the behavioral and biological bases of the effects of cholecystokinin octapeptide (CCK-8) on the rat's responses to food. The behavioral basis will be investigated by using appetitive as well as consummatory measures of motivated behavior. The appetitive measure is the running speed to very small food rewards in a meter-long runway, where postingestional effects are negligible. The consummatory measure is the amount of food ingested in a one-hour intake test in the animal's home cage. The consummatory measure gets at the satiety effects of CCK and the appetitive measure at the effects of CCK on taste-responsiveness taste reward, and the incentive value of foods. The biological basis will be investigated by pursuing our previous findings that exogenous CCK has both peripheral (intraperitoneal or i.p.) and central (intracerebroventricular or ICV) effects on satiation and on food rewards (1,2). To explore these effects further, prefeeding will be combined with peripheral or central CCK administration, testing the hypothesis that the effective dose in each route of administration will be lowered by prefeeding and a second hypothesis that subthreshold i.p. and ICV CCK doses will be additive and thus effective when given together. To explore the neural substrate, the locus of ICV injection will be varied from the anterior ventricles (third and lateral) to the fourth ventricle. In addition, specific sites in the brain will be investigated by lesioning those sites and by direct injection of CCK or the CCK-blocker, proglumide, in order to determine whether central (and where appropriate, peripheral) effects of CCK may be enhanced or diminished. In the study of the satiating effect of CCK, food-deprived rats will be used and the sites to be explored will include the area postrema (AP) and the paraventricular nuclei (PVN). In the study of the effects of CCK on taste reward and incentive effectiveness, food-satiated rats will be used to investigate sites in the limbic taste pathway, including the rostral region of the nucleus of the solitary tract (rostral NTS), the parabrachial nuclei (PBN) in the pontine taste area, the lateral hypothalamus (LH), and the central nucleus of the amygdala (CNA). By elucidating CCK's effects on both appetitive and consummatory aspects of the motivation toward food we will contribute to the theory of motivation, and also gain a better understanding of the behavioral and biological processes that go awry in the eating disorders.
NIH ExPorter
NIH ExPorter