Dissertations, Theses, and Capstone Projects

Date of Degree

9-2022

Document Type

Dissertation

Degree Name

Ph.D.

Program

Psychology

Advisor

Jeff Beeler

Committee Members

Carolyn Pytte

Allyson Friedman

Susana Mingote

Saleem Nicola

Nesha Star Burghardt

Subject Categories

Behavioral Neurobiology | Other Food Science

Keywords

Dopemine, appetite, nucleus accumbens

Abstract

Reduced dopamine (DA) signaling has been hypothesized to induce compulsive overeating in obesity. However, DA signaling facilitates food pursuit by acting on direct and indirect pathways. This disparity between why individuals compulsively overeat despite decreased DA and satiety signals is unclear. Characterizing how DA and direct/indirect pathways respond to satiation may elucidate how satiety signals become overwritten in obesity. The food's palatability may underlie this, which is putatively thought to override the satiety hormones since it directly increases DA signaling, resulting in the increased appetitive drive. We determined the pattern of dopamine and pathway-specific medium spiny neuron (MSN) activity across satiation. We used fiber photometry with a red-shifted fluorescent dopamine sensor (RdLight1) and a Cre recombinase-dependent, green calcium indicator. Both fluorescent sensors were injected into mice expressing dopamine D1 receptor (D1-Cre) or adenosine A2a receptor (Adora-Cre) (markers of direct MSNs and indirect MSNs, respectively). This straightforward approach allows for the simultaneous recordings of both DA and pathway-specific MSN activity across satiation. We measured satiation and satiety using a free-feeding paradigm. This paradigm is designed so that mice directly control their eating patterns. We confirmed that DA and MSN activity changes as a result of satiation by altering hunger and satiation via fasting and pharmacologically activating satiation areas. These studies directly measure changes in DA and d/iMSN activity from when mice are hungry to when mice become sated. We predicted that a reduced food approach would correlate with reduced DA release and dMSN activity during satiation. Also, we assessed the extent to which food's palatability overrides satiety in real-time. Using the same preparation, we examined the effects of food palatability, standard grain vs. high-fat, high sugar (HFHS) pellets, on diminishing satiation across one week. We found that repeated exposure to highly palatable foods did not delay satiation but did correlate with DA release changes. Our findings may expand our understanding on two levels: First, uncovering the dynamic changes in striatal signaling under satiation, and second, improving our understanding of the effect of palatable foods on food consumption and satiation.

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