Chronic cannabinoid exposure produces tolerance to the dopamine releasing effects of WIN 55,212-2 and heroin in adult male rats.
Chronic cannabinoid exposure produces tolerance to the dopamine releasing effects of WIN 55,212-2 and heroin in adult male rats.
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DOI：
10.1016/j.neuropharm.2020.108374
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发表时间：
2021-01
影响因子：
4.7
通讯作者：
Oleson EB
中科院分区：
文献类型：
--
作者：
Gomez DM;Everett TJ;Hamilton LR;Ranganath A;Cheer JF;Oleson EB
合成大麻素于2008年被引入娱乐性药物文化，并迅速成为美国最常滥用的药物之一。合成大麻素重复暴露所导致的神经生物学后果仍然知之甚少。多巴胺（DA）反应迟钝可能会导致吸毒者消耗更大的剂量来补偿这种形式的神经化学耐受性。由于内源性大麻素和阿片类药物系统表现出相当大的串扰和交叉耐受性经常开发后，重复暴露于阿片类药物或大麻素，有兴趣调查是否合成大麻素暴露的历史影响海洛因的能力，以增加DA释放。为了测试慢性大麻素暴露对大麻素和海洛因诱发的DA释放的影响，使用静脉内（IV）剂量递增方案（0.2- 0.8mg/kg IV，9次处理）用媒介物或合成大麻素（WIN 55 -212-2; WIN）处理雄性成年大鼠。正如所预测的，与溶剂处理对照组相比，WIN-treated大鼠在所有行为/生理测量中显示出剂量-反应关系的显著变化。然后，使用快速扫描循环伏安法来测量清醒和自由移动的大鼠的延髓核壳中的瞬时DA事件的频率的变化，观察到WIN和海洛因的DA释放效应在具有大麻素暴露的药理学历史的雄性大鼠中显著降低。这些结果表明，重复暴露于合成大麻素WIN可以产生耐受其DA释放作用和交叉耐受海洛因的DA释放作用。
Synthetic cannabinoids were introduced into recreational drug culture in 2008 and quickly became one of the most commonly abused drugs in the United States. The neurobiological consequences resulting from synthetic cannabinoid repeated exposure remain poorly understood. It is possible that a blunted dopamine (DA) response may lead drug users to consume larger quantities to compensate for this form of neurochemical tolerance. Because the endogenous cannabinoid and opioid systems exhibit considerable cross-talk and cross-tolerance frequently develops following repeated exposure to either opioids or cannabinoids, there is interest in investigating whether a history of synthetic cannabinoid exposure influences the ability of heroin to increase DA release. To test the effects of chronic cannabinoid exposure on cannabinoid- and heroin-evoked DA release, male adult rats were treated with either vehicle or a synthetic cannabinoid (WIN55-212-2; WIN) using an intravenous (IV) dose escalation regimen (0.2–0.8 mg/kg IV over 9 treatments). As predicted, WIN-treated rats showed a rightward shift in the dose-response relationship across all behavioral/physiological measures when compared to vehicle-treated controls. Then, using fast-scan cyclic voltammetry to measure changes in the frequency of transient DA events in the nucleus accumbens shell of awake and freely-moving rats, it was observed that the DA releasing effects of both WIN and heroin were significantly reduced in male rats with a pharmacological history of cannabinoid exposure. These results demonstrate that repeated exposure to the synthetic cannabinoid WIN can produce tolerance to its DA releasing effects and cross-tolerance to the DA releasing effects of heroin.
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