Behavioral sensitization following repeated intravenous nicotine administration: Gender differences and gonadal hormones
Behavioral sensitization following repeated intravenous nicotine administration: Gender differences and gonadal hormones
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DOI：
10.1016/s0091-3057(99)00169-0
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发表时间：
1999-12-01
影响因子：
3.6
通讯作者：
Mactutus, CF
中科院分区：
文献类型：
--
作者：
Booze, RM;Welch, MA;Mactutus, CF
众所周知，重复间歇性给予兴奋剂可在雄性动物中产生行为敏化。本研究探讨了1）IV给药途径是否发生行为致敏，2）雌性大鼠的致敏性是否高于雄性大鼠，3）致敏性是否受性腺切除术调节，4）完整成年雌性大鼠对重复尼古丁给药的反应是否维持正常发情期细胞学模式，以及5）IV尼古丁给药的药代动力学。成年雄性、雌性、去势和卵巢切除的Sprague-Dawley大鼠（n = 48）通过手术植入静脉输液港。动物接受50 μ g/kg IV尼古丁，每天一次，持续14天。在初始尼古丁注射和第14天最后一次尼古丁注射后，立即将动物置于IR光电池活性室中60 min。同时由对给药条件不知情的观察者进行行为观察时间采样。在IV尼古丁注射的14天时间过程中，行为活动增加超过120%。增加的幅度，但是，不同的功能组件的活动，性别和性腺切除术。行为观察数据进一步表明，雌性动物对重复尼古丁的敏感性增加，表现为更快速的反应，例如梳理毛发。这些行为观察结果与尼古丁的动脉峰值水平（类似于25 ng/ml）相关，其不高于吸烟者通常维持的尼古丁平均静脉水平。重复IV给予尼古丁（剂量为50 μ g/kg）不会干扰完整的雌性阴道细胞学或体重;未检测到此类变化并非由于统计学把握度不足。此外，尼古丁给药动物均未表现出持续阴道发情或无周期性。总的来说，这些数据表明IV尼古丁模型在探索尼古丁的性别依赖性效应方面可能特别有用。(C)1999 Elsevier Science Inc.
Repeated intermittent administration of stimulants is well known to produce behavioral sensitization in male animals. The present studies explored whether 1) behavioral sensitization occurred with the IV route of administration, 2) sensitization was greater in females than in males, 3) sensitization was modulated by gonadectomy, 4) intact adult female rats maintained normal estrous cytology patterns in response to repeated nicotine administration, and 5) the pharmacokinetics of IV nicotine dosing. Adult male, female, castrated, and ovariectomized Sprague-Dawley rats (n = 48) were surgically implanted with an intravenous access port. Animals received 50 mu g/kg IV nicotine once/day for 14 days. Immediately after the initial nicotine injection and the final day 14 nicotine injection, animals were placed in IR photocell activity chambers for 60 min. Observational time sampling of behavior was also simultaneously performed by an observer blind to treatment condition. An increase in behavioral activity of greater than 120% occurred across the 14-day time course of IV nicotine injections. The magnitude of the increase, however, varied as a function of component of activity, gender, and gonadectomy. The behavioral observation data further suggested that the females demonstrated an increased sensitivity to repeated nicotine, as evidenced in a more rapid response, for example, grooming. These behavioral observations were associated with peak arterial levels of nicotine (similar to 25 ng/ml) no greater than the average venous levels of nicotine commonly maintained by cigarette smokers. Repeated IV nicotine, at a dose of 50 mu g/kg, did not interfere with intact female vaginal cytology or body weight; the failure to detect such alterations were not due to inadequate statistical power. Moreover, no nicotine-treated animals displayed persistent vaginal estrous or were acyclic. Collectively, these data suggest that the IV nicotine model may be particularly useful in exploring the gender-dependent effects of nicotine. (C) 1999 Elsevier Science Inc.