Rationale

High rates of comorbid tobacco and cannabis use in adolescents and young adults may be related to functional interactions between the nicotinic cholinergic and cannabinoid systems in the brain during development. This study examined the effects of chronic exposure to nicotine (the psychoactive component in tobacco) on acute exposure to delta-9-tetrahydrocannabinol (THC) (the psychoactive component of cannabis).

Methods

Male and female adolescent and adult Sprague-Dawley rats (N = 112) were injected daily with nicotine (1 mg/kg, i.p.) or vehicle for 14 days, followed by a 14-day drug-free period. On test day, rats were injected with THC (5 mg/kg, i.p.) or vehicle, locomotor activity was recorded for 2 h, and brains harvested for c-Fos immunoreactivity (IR).

Results

Locomotor activity and c-Fos IR changes induced by THC challenge were altered by nicotine pre-exposure and modified by age and sex. THC-induced suppression of locomotor activity was attenuated by nicotine pre-exposure in adult but not adolescent males. THC-induced suppression of locomotor activity was potentiated by nicotine pre-exposure in female adolescents, with no effects of THC or nicotine observed in female adults. THC increased c-Fos IR in the caudate, nucleus accumbens, stria terminalis, septum, amygdala, hypothalamus, and thalamus. Nicotine pre-exposure potentiated this effect in all regions. Several brain regions showed age and sex differences in c-Fos IR such that expression was greater in adults than adolescents and in females than males.

Conclusions

Chronic nicotine pre-exposure produces lasting effects on cannabinoid-mediated signalling in the brain and on behaviour that are mediated by age and sex.

Funding support

NSERC.

中文翻译：

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慢性尼古丁暴露对雄性和雌性青春期和成年大鼠中Δ9-四氢大麻酚诱导的运动活动和神经激活的影响。

基本原理

青少年使用烟叶和大麻的高发病率可能与发育过程中大脑中烟碱胆碱能系统和大麻素系统之间的功能相互作用有关。这项研究研究了长期暴露于尼古丁（烟草中的精神活性成分）对急性暴露于delta-9-tetrahydrocannabinol（THC）（大麻的精神活性成分）的影响。

方法

雄性和雌性青春期和成年Sprague-Dawley大鼠（N  = 112）每天注射尼古丁（1 mg / kg，ip）或赋形剂，持续14天，然后停用14天。在试验当天，给大鼠注射THC（5 mg / kg，ip）或赋形剂，记录其运动能力2小时，并收集大脑的c-Fos免疫反应性（IR）。

结果

暴露于尼古丁并改变了年龄和性别，从而改变了THC激发引起的自发活动和c-Fos IR变化。在成年男性中烟碱预暴露减弱了THC诱导的运动能力抑制，而在成年男性中则没有。在女性青少年中，尼古丁预暴露可增强THC诱导的运动能力抑制，而在女性中未观察到THC或尼古丁的影响。THC增加了尾状，伏隔核，终末纹，隔层，杏仁核，下丘脑和丘脑的c-Fos IR。尼古丁预暴露可在所有地区增强这种作用。几个大脑区域在c-Fos IR中显示出年龄和性别差异，因此成年人中的表达高于青少年，女性中的表达高于男性。

结论

慢性尼古丁预暴露对大麻素介导的大脑信号传导以及由年龄和性别介导的行为产生持久影响。

资金支持

NSERC。