DOPAMINE-RECEPTOR GENE-EXPRESSION IN AN ANIMAL-MODEL OF BEHAVIORAL-DEPENDENCE ON ETHANOL

The steady-state levels of messenger RNA (mRNA) of five cloned dopamin e (D) receptors were measured in five brain regions in rats in a recen tly developed animal model of 'behavioral dependence' on ethanol. One group of rats was given the choice between ethanol and water over a 9- month period and developed 'behavioral dependence' on ethanol (group a ). This group was compared with a group given the choice between ethan ol and water for only 2 months (not yet behaviorally dependent, group b), a group forced to consume ethanol as sole fluid over a 9-month per iod (not behaviorally dependent, group c) and ethanol-naive control ra ts. All groups were sacrificed 1 month after ethanol withdrawal. The c oncentrations of mRNA of D-3-receptors in the limbic forebrain (which included the nucleus accumbens) were significantly lowered in groups a and b, but unchanged in group c. D-3 mRNA levels were reduced in the hippocampus of group b and unchanged in the cortex, amygdala and stria tum. No significant changes in the mRNA concentrations of D-1-, D-2-, D-4- or D-5-receptors were seen in the five brain regions in any group . In conclusion, chronic consumption of ethanol under the 'free-choice condition', which may best induce the drug-rewarding effect, leads to specific changes in the D-3-receptor gene expression which were not s een after forced ethanol administration. Changes in D-3 mRNA levels we re, however, not a specific correlate of 'behavioral dependence', as t hey were also detected in rats not yet 'behaviorally dependent' (group b). (C) 1997 Elsevier Science B.V.