Corrigall W A, Coen K M
Addiction Research Foundation, Toronto, Ontario, Canada.
Psychopharmacology (Berl). 1989;99(4):473-8. doi: 10.1007/BF00589894.
Intravenous nicotine maintained substantial responding on the drug-reinforced lever with a limited-access, fixed-ratio 5 schedule of self-administration. Responding demonstrated the expected pharmacological sensitivity; it was dose-dependently reduced by pre-session treatment with either nicotine or mecamylamine but not with hexamethonium. In addition, responding was dependent on the size of the unit dose, with maximum values occurring at 0.01 and 0.03 mg/kg/infusion. Self-administration behavior decreased at doses both above and below these, and extinction followed the substitution of saline for nicotine. Total session drug intake increased with unit dose up to a maximal value of approximately 0.5 mg/kg at 0.03 mg/kg/infusion, but did not increase further at the 0.06 mg/kg/infusion dose. A decrease in the time-out duration at the dose of 0.03 mg/kg/infusion also did not change the total session intake of nicotine. It is suggested that nicotine intake is controlled both by the total amount of drug obtained and by the magnitude of the unit dose. These results demonstrate that intravenous nicotine can maintain substantial self-administration behavior in rodents.
静脉注射尼古丁在药物强化杠杆上维持了大量反应，采用有限接触、固定比率5的自我给药方案。反应表现出预期的药理学敏感性；在给药前用尼古丁或美加明治疗可使其剂量依赖性降低，但六甲铵则无此作用。此外，反应取决于单位剂量的大小，在0.01和0.03mg/kg/输注时出现最大值。在这些剂量之上和之下，自我给药行为均减少，用生理盐水替代尼古丁后出现消退。每次给药的总药物摄入量随单位剂量增加，在0.03mg/kg/输注时达到约0.5mg/kg的最大值，但在0.06mg/kg/输注剂量时不再增加。在0.03mg/kg/输注剂量下减少超时持续时间也未改变尼古丁的每次给药总摄入量。提示尼古丁摄入量受获得的药物总量和单位剂量大小的控制。这些结果表明静脉注射尼古丁可在啮齿动物中维持大量的自我给药行为。
