Sex differences in tolerance to the locomotor depressant effects of lobeline in periadolescent rats.
Sex differences in tolerance to the locomotor depressant effects of lobeline in periadolescent rats.
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DOI：
10.1016/j.pbb.2009.09.009
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发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Van Horn ML
中科院分区：
文献类型：
--
作者：
Harrod SB;Van Horn ML
洛贝林正在临床试验中作为一种药物治疗甲基苯丙胺滥用和注意力缺陷多动障碍。临床前研究表明，红血球碱除了具有治疗作用外，还会引起运动障碍；然而，缺乏活动或对其运动抑制作用的耐受性的发展存在性别差异的假设尚未得到调查。青春期前后大鼠注射生理盐水以测定基线运动活动。连续7天（出生后29-35天），每天给予生理盐水或洛贝林（1.0-10 mg/kg），并在24小时后给予生理盐水以评估基线活动。Lobeline在总水平活性和中心移动距离上产生低活性。两种方法均观察到对红叶碱诱导的低活跃性的耐受性和红叶碱耐受性的性别差异。雌性对莲叶碱5.6 mg/kg的耐受性比雄性慢。盐水刺激在两项测量中显示出线性剂量依赖的多动趋势，这表明大鼠在最后的洛贝林治疗后24小时表现出运动行为的改变。这些发现证明了青春期前对红叶碱的低活性反应的性别差异，并表明女性可能比男性经历更多的运动抑制作用。慢性红血碱在停止治疗后可引起多动症。
Lobeline is being tested in clinical trials as a pharmacotherapy for methamphetamine abuse and attention deficit hyperactivity disorder. Preclinical research demonstrates that lobeline produces locomotor hypoactivity apart from its therapeutic effects; however, the hypothesis that there are sex differences in hypoactivity or in the development of tolerance to its locomotor depressant effects has not been investigated. Periadolescent rats were injected with saline to determine baseline locomotor activity. Animals received saline or lobeline (1.0–10 mg/kg) daily for 7 consecutive days (post natal days 29–35), and were challenged with saline 24 h later to assess baseline activity. Lobeline produced hypoactivity in total horizontal activity and center distance travelled. Tolerance developed to the lobeline-induced hypoactivity and sex differences in lobeline tolerance were observed on both measures. Females acquired tolerance to lobeline 5.6 mg/kg at a slower rate than males. Saline challenge revealed a linear dose-dependent trend of hyperactivity on both measures, which indicates that rats exhibited altered locomotor behavior 24 h after the final lobeline treatment. These findings demonstrate sex differences in the hypoactive response to lobeline prior to puberty and suggest that females may experience more locomotor depressant effects than males. Chronic lobeline may induce hyperactivity following cessation of treatment.
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