INVESTIGATING SEX DIFFERENCES IN THE TRANS-SYNAPTIC REGULATORS OF MESOLIMBIC DRIVEN PALATABLE FOOD INTAKE

Food intake is a coordination of elaborate sensory and motor actions that are influenced by multiple internal and external determinants but when dysregulated can result in feeding pathology. The overconsumption of highly palatable food is an important component of obesity, binge-eating disorder, and bulimia. Women and men observably experience differences in these diseases, underscoring a gap in understanding sex differences as a neurobiological factor that impacts motivated feeding behavior. In our pre-clinical studies, we employed a within-session behavior economics paradigm to tease apart several measurements of demand: hedonic set point (Q0), demand elasticity (α), P Max (elasticity defense), and essential value (reinforcement strength) of high-fat and standard food in free feeding and mildly restricted contexts in female and male mice In addition, we evaluated the effects of an anti-obesity drug, phentermine on these motivated feeding parameters. In our hedonic feeding conditions, we observed demand values are affected differently depending on sex and diet or a main effect of sex. In our homeostatic feeding conditions, we observed that the effects on the demand values were driven individually by factors of either sex or background feeding diet. During phentermine administration we observed similar trends in striking decreases in overall high-fat food demand in both sexes, but notably the reinforcement strength of the palatable food reward was not as steeply affected in female mice as seen in the male mice. In our circuitry experiments, we utilized a dual viral trans-synaptic strategy to trace upstream afferents of the mesolimbic pathway in male and female rats. Surprisingly these experiments revealed different afferent pathways in male and female groups. Female afferents of the mesolimbic pathway were labeled: BNST  VTA  NAcSh, while male afferents labeled: LSN + BNST  VTA  NAcSh. Furthermore, in situ hybridization analyses showed different estrogen receptor α distributions in the LSN and BNST in male and female that perhaps complement our palatable food intake studies of estrogen infusion into the LSN. In a cumulative analysis of these studies, we contend that mesolimbic driven motivated feeding behavior is potentially differently expressed as a result of sex dependent dimorphic hedonic circuitry.

Name thesis:degree_name

Human Pathophysiology and Translational Medicine (Doctoral)

Discipline thesis:degree_discipline

Neuroscience

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2023

Author dc:creator

• Ogunseye, Kehinde Olusola

Advisor dc:contributor.advisor

• Hommel, Jonathan (jdhommel@utmb.edu)

Committee members dc:contributor.committeemember

• Spencer, Sade
• Houghton, David
• Buffington, Shelly
• Anastasio, Noelle

Language dc:language.iso

English

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12486

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12486