Strain Specific Synaptic Modifications on Ventral Tegmental Area Dopamine Neurons After Ethanol Exposure

Biological Psychiatry Article in Press, 31 December 2008

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.

Ethanol exposure increased γ-aminobutyric acid (GABA) release onto VTA dopamine neurons in DBA mice, as previously observed in C57 mice. However, a single ethanol exposure reduced α-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.

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.

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