The effects of changing artificial cerebrospinal fluid glucose concentration on dopamine neurotransmission in the nucleus accumbens

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Marianne Hurtado-Córsico (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Steven Fordahl

Abstract: Studies have revealed that diets high in saturated fats are linked to alterations in the dopaminergic reward system that ultimately impede normal satiety signals responsible for regulating homeostatic food intake. High saturated fat (HF) consumption has also been shown to play a role in the development of a metabolic syndrome-like phenotype characterized by weight gain, insulin resistance and chronic inflammation. Further, long-term intake of a high saturated fat diet diminishes dopamine release and reuptake and impairs dopamine receptor signaling in the nucleus accumbens (NAc), which could result in overeating as a means of stimulating the dopamine pathway. The specific physiological mechanisms by which HF intake blunts dopamine neurotransmission to influence food behaviors have not been fully characterized. However, one such aspect could involve dopaminergic neuronal responses to glucose, given that neurons of the NAc have been characterized as glucose-responsive. Moreover, previous data from our lab revealed that metabolic state (as dictated by a 12-h fast) could impact synaptic control of dopamine. We therefore sought to determine whether a HF diet, in contrast to a standard low fat (LF) diet, would differentially alter dopamine neurotransmission in the NAc in response to changes in glucose concentrations and whether changes were noticeably different between NAc subregions. Results presented herein suggest that in HF animals, neuronal energy requirements for energetically demanding phasic release in the NAc core are being met by other substrates other than glucose. Moreover, enhanced tonic and phasic release in the core of LF males but not HF could indicate decreased sensitivity of glucose-responsive neurons in HF animals. Noticeable differences in treatment effect between males and females are also suggestive of sex-based differences in metabolic circuitry and energy balance, as well as alterations in estrus cycling in females due to consumption of a HF diet. Lastly, we report higher baseline dopamine release in the NAc core compared to the shell, as well as enhancements in phasic release after exposure to hypoglycemic conditions that intimate a negative energy state might prime reward-seeking behaviors in the core by preferentially enhancing phasic dopamine release. Overall, negative energy states could promote increased food-seeking and hyperphagia resulting from changes in dopamine neurotransmission within NAc subregions. Ultimately, given that food intake relies on an elaborate interplay of signaling mechanisms and other stimuli, further evaluation of changes in feeding behavior resulting from alterations in dopamine neurotransmission in the NAc are warranted, particularly in relation to metabolic states.

Additional Information

Publication
Thesis
Language: English
Date: 2023
Keywords
Dopamine neurochemistry, Food intake, HF diet, Nucleus accumbens, Obesity, Reward
Subjects
Blood glucose
Cerebrospinal fluid
Dopaminergic neurons
Nucleus accumbens

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