Matsuzawa S, Suzuki T, Misawa M, Nagase H
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Brain Res. 1998 Aug 24;803(1-2):169-77. doi: 10.1016/s0006-8993(98)00679-9.
The purpose of this study was to establish the ethanol-induced place preference in rats exposed to foot shock stress using the conditioned place preference paradigm. We also investigated the role of the endogenous opioid system in the development of the ethanol-induced place preference. The administration of ethanol (300 mg/kg, i.p.) with foot shock stress, but not without such stress, induced a marked and significant place preference. Naloxone (1 and 3 mg/kg, s.c.), a non-selective opioid receptor antagonist, significantly attenuated the ethanol-induced place preference. Moreover, the selective mu-opioid receptor antagonist beta-funaltrexamine (3 and 10 mg/kg, i.p.) and selective delta-opioid receptor antagonist naltrindole (1 and 3 mg/kg, s.c.), but not the selective kappa-opioid receptor antagonist nor-binaltorphimine (1 and 3 mg/kg, i.p.), significantly attenuated the ethanol-induced place preference. Furthermore, 150 mg/kg ethanol (which tended to produce a place preference, although not significantly) combined with each dose (that did not produce a place preference) of the mu-opioid receptor agonist morphine (0.1 mg/kg, s.c.) or 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.), but not the selective kappa-opioid receptor agonist trans-3, 4-dichloro-N-(2-(1-pyrrolidinyl)cyclohexyl)benzenacetamide methanesulfonate (U50,488H; 1 mg/kg, s.c.), produced a significant place preference. These data indicate that stress may be important for development of the rewarding effect of ethanol, and that mu- and delta-opioid receptors may be involved in the rewarding mechanism of ethanol under stressful conditions.
本研究的目的是使用条件性位置偏爱范式，在遭受足部电击应激的大鼠中建立乙醇诱导的位置偏爱。我们还研究了内源性阿片系统在乙醇诱导的位置偏爱形成中的作用。给予乙醇（300毫克/千克，腹腔注射）并施加足部电击应激，而非不施加应激时，会诱导出显著的位置偏爱。纳洛酮（1和3毫克/千克，皮下注射），一种非选择性阿片受体拮抗剂，显著减弱了乙醇诱导的位置偏爱。此外，选择性μ-阿片受体拮抗剂β-芬太尼（3和10毫克/千克；腹腔注射）和选择性δ-阿片受体拮抗剂纳曲吲哚（1和3毫克/千克，皮下注射），而非选择性κ-阿片受体拮抗剂 nor-苄基托啡（1和3毫克/千克，腹腔注射），显著减弱了乙醇诱导的位置偏爱。此外，150毫克/千克乙醇（虽未显著诱导出位置偏爱，但有此倾向）与μ-阿片受体激动剂吗啡（0.1毫克/千克；皮下注射）或选择性δ-阿片受体激动剂2-甲基-4aα-（3-羟基苯基）-1,2,3,4,4a,5,12,12aα-八氢喹啉并[2,3,3-g]异喹啉（TAN-6７；20毫克/千克，皮下注射）的各剂量（未诱导出位置偏爱）联合使用时，会产生显著的位置偏爱，而选择性κ-阿片受体激动剂反式-3,4-二氯-N-（2-（1-吡咯烷基）环己基）苯乙酰胺甲磺酸盐（U50,488H；1毫克/千克，皮下注射）则不会。这些数据表明，应激可能对乙醇奖赏效应的形成很重要，并且μ-和δ-阿片受体可能参与了应激条件下乙醇的奖赏机制。
