Background
Genetic factors and previous alcohol experience influence alcohol consumption in both humans and rodents. Specifically, a prior experience with ethanol increases ethanol intake in both ethanol-preferring C57BL/6 (C57) and ethanol non-preferring DBA/2 (DBA) mice. Whereas the ventral tegmental area (VTA) importantly regulates dopamine levels and ethanol intake, it is unknown whether ethanol experience differentially alters synaptic properties of VTA dopamine neurons in ethanol-preferring and non-preferring mice.
Conclusions
A single ethanol exposure selectively reduced glutamate receptor function in VTA dopamine neurons from the ethanol non-preferring DBA strain but enhanced GABA signaling in both C57 and DBA strains. These results support the notion that VTA dopamine neurons are a central target of ethanol-induced neural plasticity, which could contribute to ethanol consumption. Furthermore, these findings highlight the possible need for specialized therapeutic interventions for alcoholism based on individual intrinsic differences.
Methods
The properties of excitatory and inhibitory inputs and the ability to elicit long-term potentiation (LTP) were assessed with whole-cell patch-clamp recordings in VTA dopamine neurons from C57 and DBA mice 24 hours after a single ethanol (2 g/kg, IP) or equivalent saline injection.
Results
Ethanol exposure increased gamma-aminobutyric acid (GABA) release onto VTA dopamine neurons in DBA mice, as previously observed in C57 mice. However, a single ethanol exposure reduced alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) function and LTP in VTA dopamine neurons from DBA but not C57 mice. Conclusions: A single ethanol exposure selectively reduced glutamate receptor function in VTA dopamine neurons from the ethanol non-preferring DBA strain but enhanced GABA signaling in both C57 and DBA strains. These results support the notion that VTA dopamine neurons are a central target of ethanol-induced neural plasticity, which could contribute to ethanol consumption. Furthermore, these findings highlight the possible need for specialized therapeutic interventions for alcoholism based on individual intrinsic differences.