Cadoni Cristina, Simola Nicola, Espa Elena, Fenu Sandro, Di Chiara Gaetano
Institute of Neuroscience, National Research Council of Italy, Italy; National Institute of Neuroscience, University of Cagliari, Italy; Centre of Excellence 'Neurobiology of Dependence', University of Cagliari, Italy.
Addict Biol. 2015 Jan;20(1):132-42. doi: 10.1111/adb.12085. Epub 2013 Aug 20.
Adolescent Cannabis exposure has been hypothesized to act as a gateway to opiate abuse. In order to investigate the role of genetic background in cannabinoid-opiate interactions, we studied the effect of Δ(9) -tetrahydrocannabinol (THC) exposure of adolescent Lewis and Fischer 344 rats on the responsiveness of accumbens shell and core dopamine (DA), as monitored by microdialysis, to THC and heroin at adulthood. Heroin reward and reinstatement by heroin priming were studied by conditioned place preference (CPP) and cognitive and emotional functions by object recognition, Y maze and elevated plus maze paradigms. THC stimulated shell DA in Lewis but not in Fischer 344 rats. Adolescent THC exposure potentiated DA stimulant effects of heroin in the shell and core of Lewis and only in the core of Fischer 344 rats. Control Lewis rats developed stronger CPP to heroin and resistance to extinction compared with Fischer 344 strain. In Lewis rats, THC exposure did not affect heroin CPP but potentiated the effect of heroin priming. In Fischer 344 rats, THC exposure increased heroin CPP and made it resistant to extinction. Lewis rats showed seeking reactions during extinction and hedonic reactions in response to heroin priming. Moreover, adolescent THC exposure affected emotional function only in Lewis rats. These observations suggest that long-term effects of Cannabis exposure on heroin addictive liability and emotionality are dependent on individual genetic background.
青少年接触大麻被认为是通向阿片类药物滥用的一个途径。为了研究遗传背景在大麻素 - 阿片类药物相互作用中的作用，我们研究了青春期的Lewis大鼠和Fischer 344大鼠接触Δ(9) - 四氢大麻酚（THC）对成年期伏隔核壳部和核心多巴胺（DA）反应性的影响，通过微透析监测其对THC和海洛因的反应。通过条件性位置偏爱（CPP）研究海洛因奖赏和海洛因激发后的复吸情况，并通过物体识别、Y迷宫和高架十字迷宫范式研究认知和情感功能。THC刺激Lewis大鼠的伏隔核壳部DA，但不刺激Fischer 344大鼠。青春期接触THC增强了海洛因对Lewis大鼠伏隔核壳部和核心的DA刺激作用，而仅增强了Fischer 344大鼠伏隔核核心的DA刺激作用。与Fischer 344品系相比，对照Lewis大鼠对海洛因产生更强的CPP且对消退有抵抗力。在Lewis大鼠中，接触THC不影响海洛因CPP，但增强了海洛因激发的作用。在Fischer 344大鼠中，接触THC增加了海洛因CPP并使其对消退有抵抗力。Lewis大鼠在消退期间表现出寻求反应，对海洛因激发有享乐反应。此外，青春期接触THC仅影响Lewis大鼠的情感功能。这些观察结果表明，接触大麻对海洛因成瘾倾向和情绪的长期影响取决于个体遗传背景。
