Weerts E M, Griffiths R R
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Drug Alcohol Depend. 1999 Feb 1;53(3):207-14. doi: 10.1016/s0376-8716(98)00130-6.
Clonidine HCl is an antihypertensive that is also sometimes used to alleviate symptoms of withdrawal during narcotics detoxification. Recently, there have been reports abuse of clonidine by methadone patients and opioid abusers. The present study evaluated the intravenous self-administration of clonidine in four baboons. Self-injections were available 24 h/day under a fixed-ratio (FR 120 or 160) schedule of injection with a 3-h timeout after each injection. Doses of clonidine (0.0001-0.056 mg/kg per injection) or its vehicle (saline) were substituted for cocaine (0.32 mg/kg) for at least 15 days. Food pellets were available continuously under a concurrent FR 30 schedule of pellet delivery. Clonidine maintained self-injection greater than its saline vehicle in all four baboons. Although self-injection of clonidine increased as a function of dose within each baboon, there were differences between baboons in the range of doses of clonidine that maintained self-injection. Doses of 0.032 or 0.056 mg/kg maintained peak mean levels of clonidine self-injection which ranged from low (3.2 injections/day) to high (> 6 injections/day) across baboons. Levels of self-injection were similar to vehicle at 0.01 mg/kg clonidine in two of four baboons. However, in the other two baboons, very low doses of clonidine (0.0001-0.001 mg/kg) maintained low to moderate levels of self-injection. Acute administration of clonidine produced signs of sedation including lip droop, drooling and sitting with eyes closed. At high doses, some toxicity was apparent: Baboons were pale and not responsive. Food intake was generally increased in a dose dependent manner. The present study indicates that clonidine functions as a positive reinforcer.
盐酸可乐定是一种抗高血压药物，有时也用于缓解戒毒期间的戒断症状。最近，有报告称美沙酮患者和阿片类药物滥用者滥用可乐定。本研究评估了四只狒狒静脉注射可乐定的自我给药情况。在固定比率（FR 120或160）注射时间表下，每天24小时可进行自我注射，每次注射后有3小时的超时。用可乐定剂量（每次注射0.0001 - 0.056毫克/千克）或其溶媒（生理盐水）替代可卡因（0.32毫克/千克）至少15天。在同时进行的FR 30食物颗粒递送时间表下，食物颗粒可随时获取。在所有四只狒狒中，可乐定维持自我注射的效果优于其生理盐水溶媒。尽管在每只狒狒中，可乐定的自我注射量随剂量增加而增加，但不同狒狒维持自我注射的可乐定剂量范围存在差异。0.032或0.056毫克/千克的剂量维持了可乐定自我注射的峰值平均水平，不同狒狒的峰值平均水平从低（每天3.2次注射）到高（> 6次注射/天）不等。在四只狒狒中有两只，0.01毫克/千克可乐定的自我注射水平与溶媒相似。然而，在另外两只狒狒中，极低剂量的可乐定（0.0001 - 0.001毫克/千克）维持了低至中等水平的自我注射。急性注射可乐定产生了镇静迹象，包括嘴唇下垂、流口水和闭眼坐着。在高剂量时，一些毒性明显：狒狒脸色苍白且无反应。食物摄入量通常以剂量依赖的方式增加。本研究表明可乐定具有正性强化作用。
