Neurobiological study on the effects of marijuana in a unique model

点击翻译按钮获取中文摘要

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.