Involvement of dopamine D-1 and D-2 receptors in the ethanol-associated place preference in rats exposed to conditioned fear stress

The present study was designed to investigate: (1) the involvement of dopam ine D-1 and D-2 receptors, and (2) the roles of these receptors and endogen ous opioid systems (endorphinergic and enkephalinergic systems) in the etha nol-induced place preference in rats exposed to conditioned fear stress usi ng the conditioned place preference paradigm. The administration of ethanol (300 mg/kg, i.p.) induced a significant place preference. The selective D- 1 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tet rahydro-1 H3-benzazepine)hydrochloride (SCH23390; 0.01 and 0.03 mg/kg, s.c. ) and the selective D-2 receptor antagonist S(-)-5-(aminosulfonyl)-N-[(1-et hyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride: 20 and 40 mg/kg, s.c.) significantly attenuated the ethanol-induced place preference. The a dministration of ethanol (75 mg/kg, i.p.) tended to produce a place prefere nce, but this effect was not significant. SCH23390 (0.03 mg/kg, s.c.) and s ulpiride (40 mg/kg, s.c.) significantly attenuated the enhancement of the e thanol (75 mg/kg, i.p.)-induced place preference produced by the mu-opioid receptor agonist morphine (0.1 mg/kg, s.c,). In addition, SCH23390 (0.03 mg /kg, s.c.) also significantly attenuated the enhancement of the ethanol (75 mg/kg, i.p.)-induced place preference produced by the selective delta-opio id receptor agonist 2-methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-octahydroquinolino[2,3,3,-g]isoquinoline (TAN-67; 20 mg/kg, s.c.). O n the other hand, sulpiride (40 mg/kg) had no significant effect on the enh ancement of the ethanol (75 mg/kg, i.p.)-induced place preference produced by TAN-67. These results suggest that D-1 and D-2 receptors may be involved in the rewarding mechanism of ethanol under psychological stress. In addit ion, D-1 receptors may participate in the rewarding effect of ethanol modul ated by the activation of mu- and delta-opioid receptors, whereas D-2 recep tors may participate in the rewarding effect of ethanol modulated by the ac tivation of mu-opioid receptors, but not in that modulated by the activatio n of delta-opioid receptors. (C) 1999 Elsevier Science B.V. All rights rese rved.