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

Abstract

According to recent WHO reports, alcohol remains the number one substance used and abused by adolescents, despite public health efforts to curb its use. Adolescence is a critical period of biological maturation where brain development, particularly the mesocorticolimbic dopamine system, undergoes substantial remodeling. These circuits are implicated in complex decision making, incentive learning and reinforcement during substance use and abuse. An appealing theoretical approach has been to suggest that alcohol alters the normal development of these processes to promote deficits in reinforcement learning and decision making, which together make individuals vulnerable to developing substance use disorders in adulthood. Previously we have used a preclinical model of voluntary alcohol intake in rats to show that use in adolescence promotes risky decision making in adulthood that is mirrored by selective perturbations in dopamine network dynamics. Further, we have demonstrated that incentive learning processes in adulthood are also altered by adolescent alcohol use, again mirrored by changes in cue-evoked dopamine signaling. Indeed, we have proposed that these two processes, risk-based decision making and incentive learning, are fundamentally linked through dysfunction of midbrain circuitry where inputs to the dopamine system are disrupted by adolescent alcohol use. Here, we test the behavioral predictions of this model in rats and present the findings in the context of the prevailing literature with reference to the long-term consequences of early-life substance use on the vulnerability to develop substance use disorders. We utilize an impulsive choice task to assess the selectivity of alcohol’s effect on decision-making profiles and conditioned reinforcement to parse out the effect of incentive value attribution, one mechanism of incentive learning. Finally, we use the differential reinforcement of low rates of responding (DRL) task to examine the degree to which behavioral disinhibition may contribute to an overall decision-making profile. The findings presented here support the proposition that early life alcohol use selectively alters risk-based choice behavior through modulation of incentive learning processes, both of which may be inexorably linked through perturbations in mesolimbic circuitry and may serve as fundamental vulnerabilities to the development of substance use disorders.

Mechanisms of Persistent Neurobiological Changes Following Adolescent Alcohol Exposure: NADIA Consortium Findings

“…AIE also has been shown to increase risky choices (Boutros et al., ; Schindler et al., , ), measured by instrumental responding for a preferred reward, even under conditions where the choice is suboptimal. Both self‐administered and intragastric AIE exposure can enhance conditioning to reward predictive cues in adulthood (Kruse et al., ; Madayag et al., ; McClory and Spear, ; Spoelder et al., ), as indicated by approach to the cue (sign‐tracking). Finally, vapor AIE exposure in female rats promoted habit‐based alcohol seeking, indicating a loss of behavioral flexibility (Barker et al., ).…”

Neurobiology of substance use in adolescents and potential therapeutic effects of exercise for prevention and treatment of substance use disorders

“…Higher activation in the anterior cingulate cortex (ACC) and cerebellum has been observed in response to alcohol cues in alcohol abusers (Brumback et al, ). These responses are supported by preclinical studies that show alcohol use disrupts inputs to the dopamine system and, the use of alcohol during adolescence alters risk‐based decision making by modulating incentive learning (Kruse, Schindler, Williams, Weber, & Clark, ).…”

Trends in the use of mind-altering drugs among European adolescents during the Great Recession

“…It is well-known that drug use and abuse during adolescence is associated with long-term deficits in neurodevelopment such as a decline in gray matter volume, dysfunctions in memory and learning ability, and neural changes (39). Previous lab-experiments on rats show that the exposure to ethanol, which is used in the preparation of solvents, reduced their response to stress and immune challenges (40), increasing their deficits in risk-decision making (41). Moreover, the rising use of cocaine and inhalants during a period of economic recession encourages us to speculate on additional potential costs for the economy driven by health costs.…”