Author(s): Alina Svitlana Rodriguez Bezruchko
Mentor(s): K. Scott Weber, Jordan Yorgason
Institution BYU
Alcohol Use Disorder (AUD) is characterized by a diminished capacity to regulate or cease alcohol consumption, resulting in the impairment of an individual’s social, occupational, and psychological functioning. This maladaptive behavior is driven by the mesolimbic dopamine reward system, wherein the brain associates specific stimuli with rewarding outcomes, reinforcing behavior that seeks to obtain these stimuli. The primary neurotransmitter implicated in this process is dopamine (DA), which is synthesized in the ventral tegmental area (VTA) and subsequently released into the nucleus accumbens (NAc). GABA neurons inhibit DA production in the VTA. It is known that acute ethanol (EtOH) consumption elevates brain and blood dopamine levels in vivo. However, ethanol (EtOH) administration to ex vivo brain slices does not induce dopamine release in the same way it does in vivo, and dopamine itself is unable to cross the blood-brain barrier. This suggests that peripheral factors play a role in modulating neuronal activity. We hypothesize that acute ethanol (EtOH) injections elevate peripheral blood dopamine levels, subsequently binding to dopamine receptors on peripheral immune cells. This binding stimulates the release of cytokines that interact with dopamine and GABA neurons in the VTA, thereby enhancing dopamine production in the brain. We will consider sex as a biological variable. This modulation of the reward pathway may contribute to the reinforcement of alcohol use disorder. This study investigates the impact of acute ethanol consumption on the peripheral immune system and its involvement in modulating the brain's reward pathway. By understanding these mechanisms, we seek to advance the development of more effective treatments for AUD.