Long term consequences of adolescent alcohol use on behavioral inhibition

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PROJECT SUMMARY Adolescence is a “vulnerable” period because certain experiences in this period lead to detrimental lasting effects. A critical example is teenage drinking which may predispose them to life-long adverse consequences including impulsivity and impaired response inhibition. In this exploratory R21 application, we propose to exploit a rodent behavioral model to begin to understand the neuronal basis of the long-term consequences of voluntary adolescent drinking on response inhibition. Using a novel behavioral task, we find that moderate voluntary intake of alcohol during adolescence causes a robust reduction in response inhibition in both male and female adult rats. Guided by basic and clinical literature suggesting that orbitofrontal cortex (OFC) and dorsal striatum (DS) are critical for action-guided learning and impulsivity, we propose two exploratory aims to begin to understand the computational and circuit-based involvement of these two regions in mediating or modulating impaired response inhibition in adults with a history of adolescent alcohol drinking. In Aim 1, we will record from multiple units and local field potentials (LFPs) simultaneously in lateral OFC and medial DS during task performance to determine if neural encoding of relevant task events and OFC-DS coordinated activity is affected in correlation with behavioral changes. In Aim 2, we will use a chemogenetic approach to manipulate OFC-DS connections to determine the potential causative role of this pathway on the sustained impact of adolescent alcohol use on adult impulsivity. Regardless of the outcome, completion of this exploratory work will provide technical and mechanistic knowledge to support future more comprehensive studies on the neuronal basis of the lasting impact of adolescent alcohol use.