Neural regulation of cocaine valuation by adolescent cannabinoid exposure



 DESCRIPTION (provided by applicant): Adolescent marijuana use is a prominent public health concern. Indeed, exposure to marijuana during adolescence is correlated with drug abuse and addiction in adulthood and predicts future cocaine abuse. Changing national attitudes on marijuana use and the resultant push for the reform of marijuana laws (23 states and the District of Columbia currently have legalized marijuana in some form) highlight a need to examine the long-term neurobiological consequences of cannabinoid exposure. I have collected preliminary data showing that adolescent exposure to a cannabinoid agonist disrupts the experience of cocaine reward in adulthood and results in cocaine-induced conditioned place aversion. These data confirm the work of others showing that cannabinoid exposure in adolescence disturbs normal brain development and produces lasting effects on behavior. In this study, we intend to utilize cutting-edge electrochemical and optogenetic techniques to investigate the effects of cannabinoid exposure in adolescence on cocaine experience and reinforcement in adulthood. Specific aim 1 utilizes pharmacological manipulations to determine if cannabinoid exposure in adolescence exerts its effects on adult cocaine experience through actions at CB1 receptors. In the same animals we will employ the electrochemical technique fast-scan cyclic voltammetry to measure whether cannabinoid exposure during adolescence changes subsecond dopamine release evoked by cocaine and cocaine-associated contextual cues and assess how cannabinoid exposure affects the initiation and escalation of cocaine self-administration. Specific aim 2 uses optogenetic tools to test whether cannabinoids alter cocaine experience through disruption of dopaminergic function. Altogether these experiments will provide novel information concerning the neural mechanisms through which cannabinoid exposure in adolescence disturbs brain development and influences cocaine reward and reinforcement in adulthood.