Effects of nicotine exposure on oral methamphetamine self-administration, extinction, and drug-primed reinstatement in adolescent male and female rats

Effects of nicotine exposure on oral methamphetamine self-administration, extinction, and drug-primed reinstatement in adolescent male and female rats
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DOI:
10.1016/j.drugalcdep.2020.107927
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发表时间:
2020-04-01
影响因子:
4.2
通讯作者:
Crawford, Cynthia A.
Crawford, Cynthia A.
中科院分区:
医学2区
文献类型:
--
作者:
Harmony, Zachary R.;Alderson, Erin M.;Crawford, Cynthia A.

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背景:青春期尼古丁暴露增加成年雄性大鼠的甲基苯丙胺(MA)摄入量;然而,关于尼古丁如何影响MA在青春期的自我给药,人们知之甚少。因此,我们评估了青春期早期或晚期尼古丁暴露对大鼠口服MA的影响。方法:146只雄性和雌性大鼠从出生后第1天(PD)开始给予生理盐水或尼古丁(0.16或0.64 mg/kg),25-PD 34(早期暴露阶段)和/或PD 35-PD 55(晚期暴露阶段)。结果:在训练过程中,雌性大鼠比雄性大鼠更多地被戳鼻孔,只有性别变量对蔗糖和MA的获得有影响,而尼古丁不受影响。在测试阶段,在早期暴露于尼古丁(0.64 mg/kg)的雌性大鼠比生理盐水处理的雌性大鼠或尼古丁处理的雄性大鼠有更多的活跃的鼻子戳。在暴露后期暴露于尼古丁(0.16 mg/kg)的大鼠在测试期间比暴露于生理盐水的大鼠更少活跃的鼻子戳。尼古丁暴露不改变雄性大鼠消退时的鼻戳反应,但在暴露早期给予雄性大鼠0.16或0.64 mg/kg尼古丁确实能减少药物诱导的恢复期大鼠的鼻戳反应。结论:青春期雌性大鼠对口服蔗糖和MA的增强作用比青春期雄性更敏感,青春期前尼古丁暴露促进雌性大鼠口服MA的自我给药。这些发现表明,青春期前使用尼古丁可能会增加十几岁女孩以后滥用MA的易感性。
Background: Adolescent nicotine exposure increases methamphetamine (MA) intake in adult male rats; however, little is known about how nicotine affects MA self-administration during the adolescent period. Therefore, we assessed whether exposing rats to nicotine during early or late adolescence affects oral MA self-administration.Methods: 146 male and female rats were treated with saline or nicotine (0.16 or 0.64 mg/kg) from postnatal day (PD) 25-PD 34 (the early exposure phase) and/or PD 35-PD 55 (the late exposure phase). Rats began an oral MA self-administration procedure on PD 35.Results: Only the sex variable, but not nicotine, affected sucrose and MA acquisition, as female rats had more nose pokes than males during training. On the test sessions, female rats exposed to nicotine (0.64 mg/kg) in the early exposure phase had more active nose pokes than saline-treated female rats or nicotine-treated male rats. Rats exposed to nicotine (0.16 mg/kg) in the late exposure phase had fewer active nose pokes during testing than rats exposed to saline. Nose poke responding during extinction was not altered by nicotine exposure, but administering nicotine (0.16 or 0.64 mg/kg) to male rats in the early exposure phase did decrease nose pokes during the drug-primed reinstatement session.Conclusions: Our results show that adolescent female rats are more sensitive to the reinforcing effects of oral sucrose and MA than adolescent males, and that preadolescent nicotine exposure enhances oral MA self-administration in female rats. These findings suggest that preteen nicotine use may increase vulnerability to later MA abuse in teenage girls.