Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats.
Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats.
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低剂量尼古丁治疗对可卡因诱导的大鼠行为可塑性的年龄依赖性影响。
DOI：
10.1007/s00213-009-1642-0
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发表时间：
2009
影响因子：
3.4
通讯作者：
Leslie,FrancesM
中科院分区：
文献类型：
--
作者：
McQuown,SusanC;Dao,JasminM;Belluzzi,JamesD;Leslie,FrancesM
青少年早期烟草使用的流行病学证据，在大麻和其他非法药物之前，已经导致了这样的假设，即尼古丁是一种“网关”药物，它使奖励途径对其他精神兴奋剂的成瘾作用敏感。低剂量尼古丁预处理的青少年和成年大鼠对随后的急性和慢性可卡因的运动反应。材料和方法青少年，出生后（P）28天，和成年人，老年P86，每天四次注射生理盐水或尼古丁（0.06 mg/kg，i. v.）。在P32和P90，大鼠分别以0、0.4和1.0mg/kg的剂量，i. v.并在习惯的或新的测试环境中监测运动活动。为了检查可卡因致敏性，用盐水或可卡因（0.4mg/kg，静脉内）处理大鼠3天，停药1天后，给予激发剂量的可卡因（0.4 mg/kg，静脉注射）。尼古丁预处理不影响急性，药物诱导的自发活动在任何年龄。然而，可卡因反应的年龄差异被观察到，青春期的动物在新的环境中表现出增强的自发活动。青少年对照组没有表现出可卡因诱导的运动敏感性，而成年人。尼古丁预处理在青春期促进的发展和表达的致敏反应重复可卡因暴露类似于盐水预处理的成年controls.ConclusionsThese观察结果表明，短暂的预处理与尼古丁，在低剂量吸入2-4支香烟，增强可卡因诱导的行为可塑性在青春期大鼠。
RationaleEpidemiological evidence of early adolescent tobacco use, prior to that of marijuana and other illicit drugs, has led to the hypothesis that nicotine is a “gateway” drug that sensitizes reward pathways to the addictive effects of other psychostimulants.ObjectiveTo test this hypothesis, we have compared the effect of a brief, low-dose nicotine pretreatment of adolescent and adult rats on subsequent locomotor response to acute and chronic cocaine.Materials and methodsAdolescents, aged postnatal day (P) 28, and adults, aged P86, were given four daily injections of saline or nicotine (0.06 mg/kg, i.v.). At P32 and P90, rats were given acute injections of cocaine (0, 0.4 or 1.0 mg/kg, i.v.) and monitored for locomotor activity in either a habituated or novel test environment. To examine cocaine sensitization, rats were treated for 3 days with saline or cocaine (0.4 mg/kg, i.v.), and, after 1 day of withdrawal, were given a challenge dose of cocaine (0.4 mg/kg, i.v.).ResultsNicotine pretreatment did not affect acute, drug-induced locomotor activity at either age. However, age differences in cocaine response were observed, with adolescent animals showing enhanced locomotor activity in the novel environment. Adolescent controls did not exhibit cocaine-induced locomotor sensitization, whereas adults did. Nicotine pretreatment during adolescence promoted the development and expression of a sensitized response to repeated cocaine exposure similar to that observed in saline-pretreated adult controls.ConclusionsThese findings show that brief pretreatment with nicotine, in a low dose comparable to that inhaled in 2–4 cigarettes, enhances cocaine-induced behavioral plasticity in adolescent rats.