Effects of a cue associated with cocaine or food reinforcers on extinction and postextinction return of behavior.

Studies of instrumental responding often include the delivery of a cue that is coincident with the delivery of the reinforcer. One purpose of this is for the cue to be removed during extinction and then presented later to assess whether responding returns (cue-induced reinstatement). In two experiments, we examined the effects of having a cue associated with reinforcement present or absent during extinction. In Experiment 1, the cue was associated with fixed ratio responding for intravenous cocaine or food pellets in one context (Context A), followed by extinction in another context (Context B), where responding produced the cue in one group but did not produce the cue in the other group. Afterward, contextual renewal was assessed with and without the cue in Context A. During extinction, a cue previously associated with cocaine reinforcement caused an increase in responding initially (an extinction burst) and throughout 16 2-hr extinction sessions, as well as weakened contextual renewal when animals were tested with the cue in Context A. In contrast, there were few detectable effects of the cue on extinction and contextual renewal when food pellets were the reinforcer. In Experiment 2, effects of a cue during extinction of progressive ratio responding were revealed with food pellets when animals showed weakened responding on the initial trials of postextinction reacquisition sessions. These experiments demonstrate that the presence of a cue associated with reinforcement during extinction may prolong responding in the short term while creating a more persistent form of extinction that resists relapse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Influence of Stress on Decision-Making: Effects of CRF and Dopamine Antagonism in the Nucleus Accumbens.

The actions of corticotropin-releasing factor (CRF) in the core of the nucleus accumbens including increasing dopamine release and inducing conditioned place preference in stress-naïve animals. However, following two-day, repeated forced swim stress (rFSS), neither of these effects are present, indicating a stress-sensitive interaction between CRF and dopamine. To ascertain the degree to which this mechanism influences integrated, reward-based decision making, we used an operant concurrent-choice task where mice could choose between two liquid receptacles containing a sucrose solution or water delivery. Following initial training, either a CRF or dopamine antagonist, α-helical CRF (9-41) and flupenthixol, respectively, or vehicle was administered intracranially to the nucleus accumbens core. Next, the animals underwent rFSS, were reintroduced to the task, and were retested. Prior to stress, mice exhibited a significant preference for sucrose over water and made more total nose pokes into the sucrose receptacle than the water receptacle throughout the session. There were no observed sex differences. Stress did not robustly affect preference metrics but did increase the number of trial omissions compared to their stress-naïve, time-matched counterparts. Interestingly, flupenthixol administration did not affect sucrose choice but increased their nosepoke preference during the inter-trial interval, increased trial omissions, and decreased the total nosepokes during the ITI. In contrast, microinjections of α-helical CRF (9-41) did not affect omissions or ITI nosepokes but produced interactions with stress on choice metrics. These data indicate that dopamine and CRF both interact with stress to impact performance in the task but influence different behavioral aspects.

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.

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.