Lamas X, Negus S S, Gatch M B, Mello N K
Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, Belmont, MA 01278, USA.
Pharmacol Biochem Behav. 1998 Jun;60(2):357-64. doi: 10.1016/s0091-3057(98)00021-5.
The effects of heroin and cocaine administered alone or in combination were examined in rats trained to discriminate either heroin (0.56 mg/kg i.p.; n = 6) or cocaine (5.6 mg/kg i.p.; n = 6) from saline. Heroin (0.032-1.8 mg/kg) substituted completely for the heroin training stimulus in all six heroin-trained rats, but failed to substitute for cocaine in any of the cocaine-trained rats. Cocaine (0.1-32 mg/kg) substituted completely for the cocaine training stimulus in all six cocaine-trained rats, and substituted for heroin in two of six heroin-trained rats. The opioid antagonist naltrexone (0.01-1.0 mg/kg) antagonized the discriminative stimulus effects of heroin, but naltrexone at doses up to 10 mg/kg had no effect on the discriminative stimulus effects of cocaine. The dopamine receptor antagonist flupenthixol (0.032-0.56 mg/kg) attenuated the discriminative stimulus effects of heroin and completely blocked the discriminative stimulus effects of cocaine. When heroin-cocaine combinations were administered to the heroin-trained rats, cocaine (1-5.6 mg/kg) did not significantly alter the mean heroin dose-effect curve. Similarly, in the cocaine-trained rats, heroin (0.1-0.56 mg/kg) did not significantly alter the mean cocaine dose-effect curve. These results suggest that combinations of heroin and cocaine usually produce discriminative stimulus effects similar to either heroin or cocaine alone.
在经过训练能够区分海洛因（腹腔注射0.56毫克/千克；n = 6）或可卡因（腹腔注射5.6毫克/千克；n = 6）与生理盐水的大鼠中，研究了单独或联合给予海洛因和可卡因的效果。海洛因（0.032 - 1.8毫克/千克）在所有六只经海洛因训练的大鼠中完全替代了海洛因训练刺激，但在任何一只经可卡因训练的大鼠中都未能替代可卡因。可卡因（0.1 - 32毫克/千克）在所有六只经可卡因训练的大鼠中完全替代了可卡因训练刺激，并且在六只经海洛因训练的大鼠中有两只替代了海洛因。阿片类拮抗剂纳曲酮（0.01 - 1.0毫克/千克）拮抗海洛因的辨别刺激效应，但剂量高达10毫克/千克的纳曲酮对可卡因的辨别刺激效应没有影响。多巴胺受体拮抗剂氟哌噻吨（0.032 - 0.56毫克/千克）减弱了海洛因的辨别刺激效应，并完全阻断了可卡因的辨别刺激效应。当将海洛因 - 可卡因组合给予经海洛因训练的大鼠时，可卡因（1 - 5.6毫克/千克）并未显著改变平均海洛因剂量 - 效应曲线。同样，在经可卡因训练的大鼠中，海洛因（0.1 - 0.56毫克/千克）并未显著改变平均可卡因剂量 - 效应曲线。这些结果表明，海洛因和可卡因的组合通常产生与单独使用海洛因或可卡因相似的辨别刺激效应。
