Oxytocin as an appetite suppressant that reduces feeding reward

Abstract

In the environment in which palatable and highly caloric foods are readily available, eating behavior is oftentimes not dictated by the necessity to replenish lacking energy, but rather by the pleasure of consumption. Centrally acting oxytocin (OT) is known to promote termination of feeding to protect internal milieu by preventing excessive stomach distension, hyperosmolality and ingestion of toxins. Initial evidence suggests that another possible role for OT in mechanisms governing food intake is to reduce consumption of select palatable tastants. This thesis explores the question whether OT is as an appetite suppressant that reduces feeding reward. The first set of experiments addresses whether OT affects intake of (a) all carbohydrates, (b) only sweet carbohydrates or (c) sweet non-carbohydrate saccharin in mice. In those studies, generalized injection of a blood brain barrier penetrant OT receptor antagonist, L-368,899, significantly increased the intake of sweet (sucrose, glucose, fructose, polycose) and non-sweet (cornstarch) carbohydrates and promoted a trend approaching significance in saccharin consumption. Consumption of carbohydrate-enriched foods led to an increase in OT mRNA levels in the hypothalamus. The second set of studies identifies the nucleus accumbens core (AcbC), a key component of the reward system, as a site that mediates anorexigenic effects of OT. Rats injected with OT directly in the AcbC showed a decreased intake of sucrose and saccharin solutions as well as of standard chow. This treatment did not cause taste aversion, hence the outcome was not due to sickness/malaise. The effects of AcbC OT on feeding could be observed only in animals offered a meal in a non-social environment. Once a social setting (devoid of direct antagonistic interactions between individuals) of a meal was introduced, AcbC OT failed to reduce feeding. AcbC levels of OT receptor transcript were affected by exposure to palatable food as well as by food deprivation. The third and final set of studies shows that aberrant integrity of neuronal circuitry within the neuroendocrine and reward systems due to genetic deletion of connexin 36 (Cx36) gap junctions leads to dysregulation of the OT system’s functioning in the Cx36 KO mouse. This dysregulation is associated with hypersensitivity to aversive properties of foods, reduced interest in feeding for reward (palatable carbohydrates and saccharin) and abnormal ingestion of energy. Overall, the findings suggest that OT diminishes feeding for reward, particularly the intake of palatable carbohydrates and saccharin, by acting – at least in part – via the reward system. OT appears to be part of central mechanisms that cross-link homeostasis-driven and palatability-related (i.e., flavor- and macronutrient-specific) termination of consumption.