Strain specific synaptic modifications on ventral tegmental area dopamine neurons after ethanol exposure.
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.


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.
Wanat
Matthew J
MJ
Neuroscience Graduate Program, University of California-San Francisco, San Francisco, California, USA.
Sparta
Dennis R
DR
Hopf
F Woodward
FW
Bowers
M Scott
MS
Melis
Miriam
M
Bonci
Antonello
A
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL / Q000378:metabolism / Q000502:physiology*; D008811:Mice, Inbred DBA / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013045:Species Specificity; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D004298:Dopamine