Adolescent Oxycodone Exposure on Oxycodone Reinforcement and Reward Neurocircuitry in Adulthood

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ABSTRACT: Adolescence is one of the most vulnerable stages for the long-term effects of drugs of abuse and an estimated 3.4 million from adolescence have misused prescription opioids in the past year, with 3.5% of them being in early/mid stage of adolescents (12 -17 years old) and 7.1% of them being in the late adolescence to emerging adulthood stage (ages 18-25) (Substance Abuse and Mental Health Services Administration, 2017). Early adolescent initiation of prescriptions opioids is more likely to result in subsequent prescription opioid misuse in adulthood than late adolescent initiation (McCabe et al., 2007). Therefore, there is a need to better understand the long-term neurobiological consequences that misuse of prescription opioids in early/mid and late adolescence may have in adulthood in order to develop unique interventions. Oxycodone is one of the most commonly misused prescription opioids among adolescents. However, there is a substantial gap in knowledge about the long-term neurobiological consequences of adolescence exposure to oxycodone on reward-related behaviors in adulthood. The use of pre-clinical animal models can help to understand the effects of adolescent exposure to oxycodone on adult mesolimbic reward pathway. The major goal of this small grant project (R03) is to obtain proof of concept data to show that adolescent oxycodone exposure leads to a persistent increase in reinforcing properties/dopamine release in adulthood. Therefore, the overall objectives are to determine the effects of early and late adolescence exposure to oxycodone on drug reinforcement and dopamine release in nucleus accumbens in adulthood and assess if there are differential effects between early and late adolescence exposure. Since the early and late adolescence drug exposure will have differential effects on the neurobiology of reward circuits due to hormonal changes (Spears, 2000; 2015), we will utilize two time-points of adolescence exposure. This proposal will utilize state-of-the-art procedures to elucidate how adolescence exposure alters reinforcing properties of oxycodone within the mesolimbic dopamine system. This is a highly significant project that will provide first data on how adolescent exposure to oxycodone will have long-lasting effects on VTA rewarding properties in adulthood. Once we establish this phenomenon in this model, the data will be used to further understand the persistent changes in reward circuitry and molecular mechanisms in future R01 application.