Authors

Ross Armant

Document Type

Honors Thesis

Abstract

Addiction is a brain disease that results from chronic enhanced activation of brain structures of the mesolimbic dopamine reward pathway by drugs of abuse. This results in long term functional changes in the brain’s reward pathway. Sex differences in behavioral responses and neuroadaptations resulting from chronic drug use have been established. These sex differences are associated with fluctuating ovarian hormone levels during the reproductive cycles of females. For example, in female rodents, estradiol influences dopamine activity within the mesolimbic reward system such that drug-directed behaviors are enhanced. The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is an important regulator of dopamine activity within the mesolimbic reward pathway. Previous studies have characterized the activity of RMTg cells after cocaine administration in male animals. The present study was conducted to determine if cocaine also activates this nucleus in female rodents and to identify sex differences in such neural activation. Adult male and female experimentally naive Long Evans rats were treated with cocaine or saline, and standard immunohistochemical techniques were used to identify c-Fos positive neurons in the RMTg. Overall, cocainetreated males and females expressed higher levels of c-Fos positive cells compared to saline-treated controls. Cocaine-treated male rats showed no significant difference in the number of c-Fos positive cells compared to cocaine-treated females, or cocaine-treated females in estrus or diestrus. Further analyses are needed to determine if sex differences are present in RMTg projections. The RMTg may be an ideal target for further preclinical, clinical, and pharmacological research for developing better addiction treatments.

Publication Date

5-1-2020

Language

English

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