Neurobiological study on the effects of marijuana in a unique model

描述（由申请人提供）：青少年使用大麻是一个突出的健康问题，可能使脆弱个体更容易患精神病和成瘾。我们和其他人已经描述了精神病和成瘾共病发展的动物模型。在这里，我将测试青少年接触大麻是否会加剧这种独特动物模型中发生的行为和神经生物学适应。有两种症状值得关注，感觉运动门控和奖励学习缺陷。我会用声惊反应的脉冲前抑制来测试感觉运动门控的缺陷；我将通过测量在先前描述的条件奖励学习任务的试验中反应延迟的变化来测试奖励学习的缺陷。这两种行为都与亚秒多巴胺信号有关。使用一种称为快速扫描循环伏安法的尖端神经化学技术，我将测量在这些行为任务中，青少年接触大麻是否会改变由声音刺激或条件刺激引起的亚秒多巴胺释放。我们检测伴随精神病症状表达的多巴胺释放的精确变化的能力将提供有关神经生物学机制的新信息，通过该机制，青少年大麻暴露可能会增加对精神病和成瘾的易感性。

DESCRIPTION (provided by applicant: Adolescent marijuana-use is a prominent health concern that may confer increased susceptibility to psychosis and addiction in vulnerable individuals. We, and others, have characterized an animal model of the co-morbid development of psychosis and addiction. Here, I will test whether adolescent marijuana exposure exacerbates behavior and neurobiological adaptations occurring in this unique animal model. Two symptoms are of interest, deficits in sensorimotor gating and reward learning. I will test for deficits in sensorimotor gating using prepulse inhibition of the acoustic startle response; I will test for deficits in reward learning by measuring changes in response-latency across trials in previously described conditioned reward learning task. Both of these behaviors are known to involve subsecond dopamine signaling. Using a cutting edge neurochemical technique called fast-scan cyclic voltammetry, I will measure whether adolescent marijuana exposure changes subsecond dopamine release evoked by either acoustic-stimuli or conditioned stimuli during performance in these behavioral tasks. Our ability to detect precise changes in dopamine release accompanying the expression of psychotic symptoms will provide novel information concerning the neurobiological mechanisms through which adolescent marijuana exposure might confer increased vulnerability to psychosis and addiction.