Adolescent alcohol use remains a major public health concern due in part to evidence implicating the age of initial alcohol use as a strong predictor fo the development of alcohol use disorders in adulthood. Recent reports evaluating the impact of drug abuse on society conclude that alcohol ranks as the most harmful of all abused substances. In addition, despite continuing efforts to curb its use, alcohol remains the most commonly used and abused substance among adolescents. That such experience can be antecedent to problem drinking has been recognized for some time; that such experience may also have long-lasting effects on decision- making processes is a relatively recent consideration. Moreover, it has been suggested that such deficits in decision making may represent a vulnerability to addiction. Indeed, people who engage in binge drinking at an early age show later deficits in decision making and increased likelihood of developing alcohol abuse problems. However, interpretation of these reports in humans has remained challenging due to the difficulty in separating the specific consequences of early drug use on future behavior from pre-existing factors that may contribute throughout the lifespan. We have demonstrated that rats exposed to alcohol during adolescence make maladaptive, risky choices as adults. This impairment represents a unique vulnerability of the developing brain as we have also shown that adult rats given identical exposure do not show this deficit. Adolescence has been characterized as a time of heightened risk-taking behavior in humans. Moreover, adolescence is a critical period of maturation when brain development, including that of the mesolimbic dopamine (DA) system, may be disrupted by alcohol. Mesolimbic DA is implicated in multiple aspects of reward processing and risk preference is sensitive to manipulations of striatal phasic DA signaling. Indeed, we have shown that striatal phasic DA release in response to risky options relative to safe options is significantly increased in alcohol-exposed rats. Further, there is a relative disinhibition in DA signaling during adolescence itself. Therefore, an appealing theoretical approach has been to link maturational changes in DA systems with behavioral changes in decision making and to posit that early life alcohol use confers a neurobiological profile that promotes persistent maladaptive decision making into adulthood. However, our findings to date are based on low levels of exposure that model recreational alcohol use while one of the defining features of use in human adolescents is a high incidence of binge drinking. Thus, in this proposal we aim to expand the scope and clinical relevance of our work by examining the consequences of binge alcohol use, which predominates in adolescence and is achieved by the NADIA AIE protocol. We hypothesize that increased risk bias, characteristic of the adolescent period, is attributable to mesolimbic DA systems and that exposure to AIE alters these circuits, resulting in a circuit-specific potentiation of midbrain DA neuron activity and persistent maladaptive decision making in adulthood.
Adolescent alcohol use is a major public health concern and is strongly correlated with the development of alcohol abuse problems in adulthood. The mesolimbic dopamine system, which undergoes an active developmental stage during adolescence, is implicated in decision making and many aspects of drug abuse. Thus, the primary goal of this proposal is to examine the hypothesis that maladaptive decision making after adolescent binge alcohol use, which results in an increased vulnerability to alcohol use disorders in adulthood, is attributable to a perturbation in mesolimbic dopamine circuitry.
| Kruse, Lauren C; Schindler, Abigail G; Williams, Rapheal G et al. (2017) Maladaptive Decision Making in Adults with a History of Adolescent Alcohol use, in a Preclinical Model, Is Attributable to the Compromised Assignment of Incentive Value during Stimulus-Reward Learning. Front Behav Neurosci 11:134 |
| Schindler, Abigail G; Soden, Marta E; Zweifel, Larry S et al. (2016) Reversal of Alcohol-Induced Dysregulation in Dopamine Network Dynamics May Rescue Maladaptive Decision-making. J Neurosci 36:3698-708 |
