Sex-specific neurobiological mechanisms of feeding, motivation, and opioid reward
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[EMBARGOED UNTIL 05/01/2026] Obesity and opioid use disorder (OUD) are two of the most pressing public health crises in the United States. While often studied separately, both are influenced by overlapping neurobiological systems involved in reward and motivation. This dissertation investigated sex differences in the (1) methodological approach to examining feeding patterns; (2) ventral striatal mechanisms underlying motivational effort for palatable food; (3) and the interaction of palatable diet and hedonic feeding on morphine-associated reward and relapse-like behaviors. In the first study, male and female rats were exposed to conditions of food deprivation and morphine administration to examine changes in diet choice between standard chow and a palatable diet. Both sexes preferred the palatable diet, but only males increased chow intake after deprivation, indicating sex-specific responses to homeostatic signals. The second study assessed the role of intra-accumbens (Acb) MCHR1 signaling in DAMGO-induced motivation for sucrose using a progressive ratio task. Intra-Acb administration of the MCHR1 antagonist SNAP-94847 blocked DAMGO's enhancement of motivational effort in females, without affecting low-effort free feeding in either sex. These findings suggest MCH modulates opioid-driven appetitive effort-based motivation specifically. The third study explored the effects of an opioid-driven model of hedonic feeding on expression of morphine conditioned place preference (CPP) and reinstatement. The opioid-driven hedonic feeding treatment reduced morphine CPP expression in males but had no effect in females, while neither treatment produced reinstatement of morphine CPP in either sex. The final study explored the influence of providing access to a palatable diet, or standard chow, on morphine CPP reinstatement, and in a separate experiment, on morphine CPP extinction. Palatable diet access, compared to chow access, prior to extinction sessions significantly prolonged the number of trials to reach morphine CPP extinction, and also induced morphine CPP reinstatement.
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Ph. D.