Neurobiological study on the effects of marijuana in a unique model

描述（由申请人提供）：青少年大麻使用是一个突出的健康问题，可能会增加易受伤害的个人对精神病和成瘾的易感性。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的特征。在这里，我将测试青少年大麻暴露是否会加剧这种独特的动物模型中发生的行为和神经生物学适应。两个症状是感兴趣的，感觉运动门控和奖励学习的缺陷。我将使用声惊吓反应的前脉冲抑制来测试感觉运动门控的缺陷;我将通过测量先前描述的条件性奖励学习任务中的反应潜伏期的变化来测试奖励学习的缺陷。已知这两种行为都涉及亚秒多巴胺信号。使用尖端的神经化学技术，称为快速扫描循环伏安法，我将测量青少年大麻暴露是否会改变亚秒多巴胺释放诱发的声学刺激或条件刺激在这些行为任务的性能。我们的能力，以检测伴随着精神病症状的表达多巴胺释放的精确变化将提供新的信息，通过青少年大麻暴露可能会增加精神病和成瘾的脆弱性的神经生物学机制。 公共卫生相关性： 根据NIDA资助的2008年监测未来研究，每年有24%的10年级学生和32.4%的12年级学生滥用大麻。这是令人震惊的，因为越来越多的文献表明，青少年接触大麻可能会增加精神病和成瘾的风险。这项拟议中的研究将提供有关青少年大麻暴露可能增加精神病和成瘾风险的神经机制的新信息。这些信息将促进未来药物治疗的发展，旨在治疗这些疾病的症状。

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. PUBLIC HEALTH RELEVANCE: According to the NIDA-funded 2008 Monitoring the Future Study, 24% of 10th graders and 32.4% of 12th graders abuse marijuana each year. This is alarming due to a growing literature suggesting that adolescent marijuana exposure may confer increased risk for psychosis and addiction. The proposed study will provide new information concerning the neural mechanisms through which adolescent marijuana exposure may increase the risk for psychosis and addiction. This information will facilitate the development of future pharmacotherapies designed to treat symptoms of these conditions.