Sex-dependent modulation of ethanol consumption in vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) knockout mice.
Several lines of evidence suggest that monoaminergic systems, especially dopaminergic and serotoninergic systems, modulate ethanol consumption. Humans display significant differences in expression of the vesicular and plasma membrane monoamine transporters important for monoaminergic functions, including the vesicular monoamine transporter (VMAT2, SLC18A2) and dopamine transporter (DAT, SLC6A3). In addition, many ethanol effects differ by sex in both humans and animal models. Therefore, ethanol consumption and preference were compared in male and female wild-type mice, and knockout (KO) mice with deletions of genes for DAT and VMAT2. Voluntary ethanol (2-32% v/v) and water consumption were compared in two-bottle preference tests in wild-type (+/+) vs heterozygous VMAT2 KO mice (+/-) and in wild-type (+/+) vs heterozygous (+/-) or homozygous (-/-) DAT KO mice. Deletions of either the DAT or VMAT2 genes increased ethanol consumption in male KO mice, although these effects were highly dependent on ethanol concentration, while female DAT KO mice had higher ethanol preferences. Thus, lifetime reductions in the expression of either DAT or VMAT2 increase ethanol consumption, dependent on sex.
Hall
F Scott
FS
Molecular Neurobiology Branch, NIDA-IRP, NIH, DHHS, Baltimore, MD, USA.
Sora
I
I
Uhl
G R
GR
D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D012727:Sex Characteristics; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C493453:Slc18a2 protein, mouse; C493215:Slc6a3 protein, mouse; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins