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 dopamine D(1) and D(2) receptors, and (2) the roles of these receptors and endogenous opioid systems (endorphinergic and enkephalinergic systems) in the ethanol-induced place preference in rats exposed to conditioned fear stress using 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-tetrahydro-1H3-benzazepine)hydrochloride (SCH23390; 0.01 and 0.03 mg/kg, s.c.) and the selective D(2) receptor antagonist S(-)-5-(aminosulfonyl)-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2- methoxybenzamide (sulpiride; 20 and 40 mg/kg, s.c.) significantly attenuated the ethanol-induced place preference. The administration of ethanol (75 mg/kg, i.p.) tended to produce a place preference, but this effect was not significant. SCH23390 (0.03 mg/kg, s.c.) and sulpiride (40 mg/kg, s.c.) significantly attenuated the enhancement of the ethanol (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-opioid receptor agonist 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12, 12aalpha-octahydroquinolino[2,3,3,-g]isoquinoline (TAN-67; 20 mg/kg, s.c.). On the other hand, sulpiride (40 mg/kg) had no significant effect on the enhancement 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 addition, D(1) receptors may participate in the rewarding effect of ethanol modulated by the activation of mu- and delta-opioid receptors, whereas D(2) receptors may participate in the rewarding effect of ethanol modulated by the activation of mu-opioid receptors, but not in that modulated by the activation of delta-opioid receptors.
Matsuzawa
S
S
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Suzuki
T
T
Misawa
M
M
Nagase
H
H
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D018492:Dopamine Antagonists / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005239:Fear; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012201:Reward; D013312:Stress, Physiological / Q000503:physiopathology
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000431:Ethanol