Corrigall W A, Herling S, Coen K M
Neurobiology Section, Addiction Research Foundation, Toronto, Ontario, Canada.
Psychopharmacology (Berl). 1988;96(1):29-35. doi: 10.1007/BF02431529.
The effects of nicotine, heroin, mecamylamine, and naltrexone were studied in rats trained to respond under a fixed-interval 3-min schedule of food presentation. Nicotine (0.1-3.0 mg/kg) first increased, then decreased response rates; heroin (0.03-0.6 mg/kg) produced only dose-related response rate decreases. Mecamylamine (0.1-3.0 mg/kg) and naltrexone (0.3-10.0 mg/kg), administered alone, each had little effect on response rates. However, when administered in combination with increasing doses of nicotine, mecamylamine (1.0 mg/kg) blocked the increases in response rate caused by 0.3 and 1.0 mg/kg nicotine and partially reversed the decreases in rate caused by 3.0 mg/kg nicotine. In contrast, the combination of naltrexone and nicotine, at doses of each that alone either had no effect or increased response rates, markedly decreased responding. This phenomenon was not evident during the first pairing of naltrexone and nicotine, but appeared in the second and subsequent pairings. After drug combinations had been tested, the nicotine dose-response curve was unchanged from its previous values, and naltrexone alone produced no tendency to decrease response rate. These observations may be related to previous results that have suggested a role for endogenous opioids in mediating certain of the behavioral effects of nicotine.
在经过训练能在固定间隔3分钟的食物呈现时间表下做出反应的大鼠中，研究了尼古丁、海洛因、美加明和纳曲酮的作用。尼古丁（0.1 - 3.0毫克/千克）首先提高然后降低反应率；海洛因（0.03 - 0.6毫克/千克）仅产生与剂量相关的反应率降低。单独给予美加明（0.1 - 3.0毫克/千克）和纳曲酮（0.3 - 10.0毫克/千克）时，它们各自对反应率几乎没有影响。然而，当与递增剂量的尼古丁联合给药时，美加明（1.0毫克/千克）阻断了0.3和1.0毫克/千克尼古丁引起的反应率升高，并部分逆转了3.0毫克/千克尼古丁引起的反应率降低。相比之下，纳曲酮和尼古丁联合使用时，在单独使用时要么无作用要么提高反应率的剂量下，显著降低了反应。这种现象在纳曲酮和尼古丁首次配对时不明显，但在第二次及后续配对时出现。在测试药物组合后，尼古丁剂量 - 反应曲线与之前的值相比没有变化，单独使用纳曲酮也没有降低反应率的趋势。这些观察结果可能与之前的研究结果有关，之前的研究结果表明内源性阿片类物质在介导尼古丁的某些行为效应中起作用。
