Abstract
BACKGROUND: Ethanol (EtOH) affects prefrontal cortex functional roles such as decision making, working memory, and behavioral control. Yet, the pharmacological effect of EtOH on dopamine, a neuromodulator in the medial prefrontal cortex (mPFC), is unclear. Past studies exploring this topic produced conflicting outcomes; however, a handful of factors (temporal resolution, method of drug administration, estrous cycle) possibly contributed to these discrepancies. We sought to mitigate these factors in order to elucidate EtOH's pharmacological effects on mPFC dopamine in Long-Evans rats. METHODS: We administered experimental solutions via an intravenous (iv), handling-free route, monitored dopamine in the mPFC via microdialysis (10-minute samples), and used male rats to avoid estrous cycle/EtOH interactions. First, we rapidly (approximately 2.7 ml/min) or slowly (approximately 0.6 ml/min) administered 1.0 g/kg EtOH and saline infusions, showing that the experimental methods did not contribute to dopamine changes. Then, a cumulative dosing protocol was used to administer 0.25, 0.75, 1.50, and 2.25 g/kg iv EtOH doses to evaluate dose-response. Finally, we monitored dialysate EtOH levels during an oral EtOH self-administration session to compare the dialysate EtOH levels achieved during the pharmacological experiments to those seen during self-administration. RESULTS: IV administration of a rapid or slow 1.0 g/kg EtOH infusion resulted in similar significant 55 ± 9 and 63 ± 15% peak dialysate dopamine increases, respectively. The 0.25, 0.75, 1.50, and 2.25 g/kg EtOH doses produced a nonsignificant 17 ± 5% and significant 36 ± 15, 68 ± 19, and 86 ± 20% peak dialysate dopamine increases, respectively. Self-administration dialysate EtOH concentrations fell within the range of concentrations noted during the EtOH dose-response curve. CONCLUSIONS: These experiments show that, using experimental methods that minimize possibly confounding factors, acute iv EtOH increases extracellular dopamine in the mPFC in a dose-dependent manner, thereby clarifying EtOH's pharmacological effects on the mesocortical dopamine system.