During adolescence, individuals often receive their first exposure to alcohol, and a significant proportion do so during episodes of high intake or bingeing. Such experience can be antecedent to problem drinking and is associated with impairments in decision making. Recently, it has been demonstrated that adolescent alcohol use is sufficient to produce long-term perturbation of risk-based decision making in rodents. Adolescence is a critical period of maturation where brain development may be disrupted by alcohol use. Specifically, the mesolimbic dopamine system has been shown to be enduringly altered by chronic alcohol exposure during adolescence. Phasic increases in dopamine are evoked by rewarding outcomes and associated cues. These signals have been shown to scale with the magnitude and probability of reward which, together with reward costs, make up the fundamental components of optimal decision making. Importantly, all of these attributes of the decision making apparatus are thought to be exploited by abused substances. Indeed, phasic dopamine signaling to risky, but not safe, options is increased in animals with a history of adolescent alcohol exposure. These findings suggest that changes in phasic dopamine release, as a consequence of alcohol exposure, could underlie biases in choice behavior and promote risk preference. Therefore, it is hypothesized that adolescent alcohol exposure influences risk preference through modulation of dopamine systems and that such modulation perturbs one or more of three fundamental elements of decision making;cost encoding, risk assessment, and/or the encoding of reward outcomes during learning. The current proposal will test these hypotheses with three specific aims.
Aim 1 will test the hypothesis that risk preference evolves from cost insensitivity where anticipated reward value is not discounted based upon the increasing cost associated with its procurement.
Aim 2 will test the hypothesis that risk preference results from diminished risk assessment and the proposition that uncertainty may paradoxically enhance value (i.e. a """"""""gambling buzz"""""""").
Aim 3 will test the hypothesis that risk preference is a consequence of the aberrant encoding of reward outcomes during reinforcement learning.
Adolescent alcohol use is a major public health concern and is strongly correlated with the development of alcohol abuse problems in adulthood. The phasic activation of the neuromodulator dopamine is implicated in reward processing, decision making, and many aspects of drug abuse. The primary goal of this proposal is to examine the contribution of phasic dopamine transmission, altered by a history of adolescent alcohol exposure, to deficits in decision making and learning that may represent vulnerabilities to the development of addictive disorders.
|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|
|Spoelder, Marcia; Tsutsui, Kimberly T; Lesscher, Heidi M B et al. (2015) Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive Cues Through Potentiation of Phasic Dopamine Signaling. Neuropsychopharmacology 40:2873-85|
|Lesaint, Florian; Sigaud, Olivier; Clark, Jeremy J et al. (2015) Experimental predictions drawn from a computational model of sign-trackers and goal-trackers. J Physiol Paris 109:78-86|
|Hart, Andrew S; Clark, Jeremy J; Phillips, Paul E M (2015) Dynamic shaping of dopamine signals during probabilistic Pavlovian conditioning. Neurobiol Learn Mem 117:84-92|
|Schindler, Abigail G; Tsutsui, Kimberly T; Clark, Jeremy J (2014) Chronic alcohol intake during adolescence, but not adulthood, promotes persistent deficits in risk-based decision making. Alcohol Clin Exp Res 38:1622-9|
|Clark, Jeremy J; Collins, Anne L; Sanford, Christina Akers et al. (2013) Dopamine encoding of Pavlovian incentive stimuli diminishes with extended training. J Neurosci 33:3526-32|
|Clark, Jeremy J; Hollon, Nick G; Phillips, Paul E M (2012) Pavlovian valuation systems in learning and decision making. Curr Opin Neurobiol 22:1054-61|
|Clark, Jeremy J; Nasrallah, Nicholas A; Hart, Andrew S et al. (2012) Altered risk-based decision making following adolescent alcohol use results from an imbalance in reinforcement learning in rats. PLoS One 7:e37357|