Ingman Kimmo, Salvadori Severo, Lazarus Larry, Korpi Esa R, Honkanen Aapo
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
Addict Biol. 2003 Jun;8(2):173-9. doi: 10.1080/1355621031000117400.
We studied the effect of a novel delta-opioid receptor antagonist N,N(CH(3))(2)Dmt-Tic-OH (Me(2)-Dmt-Tic-OH) on voluntary ethanol intake in an alcohol-preferring AA (Alko, Alcohol) rat line using a 4-hour limited access paradigm. Acute injections of Me(2)-Dmt-Tic-OH (10 and 30 mg/kg, i.p.) did not reduce 1-hour or 4-hour ethanol intake. Subtype non-selective opioid receptor antagonist naltrexone [0.1 and 0.3 mg/kg, subcutaneously (s.c.)] significantly reduced 1-hour ethanol drinking but had no effect on 4-hour ethanol consumption. Locomotor stimulation induced by the delta-opioid receptor agonist Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE; 15 microg, intracerebroventricularly) was significantly attenuated by Me(2)-Dmt-Tic-OH (10 and 30 mg/kg, i.p.), which confirmed its efficacy as a delta-opioid receptor antagonist in rat brain. Our results support the idea that delta-opioid receptors do not mediate alcohol reward in AA rats.
我们使用4小时有限接触范式，研究了新型δ-阿片受体拮抗剂N,N(CH(3))(2)Dmt-Tic-OH（Me(2)-Dmt-Tic-OH）对酒精偏好型AA（阿尔科，酒精）大鼠品系自愿乙醇摄入量的影响。急性注射Me(2)-Dmt-Tic-OH（10和30毫克/千克，腹腔注射）并未减少1小时或4小时的乙醇摄入量。非选择性阿片受体拮抗剂纳曲酮[0.1和0.3毫克/千克，皮下注射]显著减少了1小时的乙醇饮用量，但对4小时的乙醇消耗量没有影响。δ-阿片受体激动剂Tyr-D-Pen-Gly-Phe-D-Pen（DPDPE；15微克，脑室内注射）诱导的运动刺激被Me(2)-Dmt-Tic-OH（10和30毫克/千克）显著减弱，这证实了其作为大鼠脑中δ-阿片受体拮抗剂的功效。我们的结果支持这样的观点，即δ-阿片受体不介导AA大鼠的酒精奖赏。
