Background
Ethanol stimulates the dopaminergic mesoaccumbal pathway, which is thought to play
a role in ethanol reinforcement. Mu (μ)-opioid (MOP) receptors modulate accumbal dopamine
activity, but it is not clear whether MOP receptors are involved in the mechanism
of ethanol-stimulated accumbal dopamine release.
Methods
We investigated the role that MOP receptors play in ethanol (2.0 g/kg)-stimulated
accumbal dopamine release by using MOP receptor knockout mice (C57BL/6J-129SvEv and
congenic C57BL/6J genotypes) along with blockade of MOP receptors with a μ1 selective
antagonist (naloxonazine).
Results
Both gene deletion and pharmacological antagonism of the MOP receptor decreased ethanol-stimulated
accumbal dopamine release compared with controls with female mice showing a larger
effect in the C57BL/6J-129SvEv genotype. However, both male and female mice showed
reduced ethanol-stimulated dopamine release in the congenic MOP receptor knockout
mice (C57BL/6J). No differences in the time course of dialysate ethanol concentration
were found in any of the experiments.
Conclusions
The data demonstrate the existence of a novel interaction between genotype and sex
in the regulation of ethanol-stimulated mesolimbic dopamine release by the MOP receptor.
This implies that a more complete understanding of the epistatic influences on the
MOP receptor and mesolimbic dopamine function may provide more effective pharmacotherapeutic
interventions in the treatment of alcoholism.
Key Words
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Article info
Publication history
Published online: March 09, 2007
Accepted:
November 14,
2006
Received in revised form:
November 13,
2006
Received:
August 2,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
