Adolescent reinforcement-learning trajectories predict cocaine-taking behaviors in adult male and female rats

Sex differences in oxycodone-taking behaviors are linked to disruptions in reward-guided, decision-making functions

“…Poor decision-making observed in female rats in the current study was surprising given that our previous studies examining decision-making functions across adolescent development in the rat have not observed decision-making differences between males and females (Moin Afshar et al, 2020; Villiamma et al, 2022). Sex differences in decision-making might, therefore, emerge during early adulthood when prefrontal circuits have stabilized (Casey et al, 2000; Galvan et al, 2006).…”

“…Choice behavior collected from rats in the PRL task was analyzed with a differential forgetting reinforcement-learning model (Barraclough et al, 2004;Ito and Doya, 2009;Groman et al, 2019a), which captures gradually decaying effects of previous choices and outcomes on choices. This model was found to fit the choice behavior of rats significantly better than other reinforcement-learning models (see Supplemental methods and Supplemental Table 1), as we have previously shown (Groman et al, 2020;Moin Afshar et al, 2022;Villiamma et al, 2022). This reinforcement-learning model contains four free parameters: a decay rate for the action values of chosen options (γ C ), a decay rate for the action values of unchosen options (γ U ), a parameter for the appetitive strength of rewarded outcomes (Δ + ), and a parameter for the aversive strength of unrewarded outcomes (Δ 0 ).…”

“…Emerging evidence suggests that decision-making could be a useful behavioral biomarker for delineating the biological mechanisms that mediate addiction susceptibility from those that are consequent to drug use (Groman and Jentsch, 2012; Groman et al, 2022). Specifically, we have found that deficits in reward-guided, decision-making prior to any drug exposure are predictive of greater cocaine-taking behaviors in rats (Groman et al, 2020; Villiamma et al, 2022) and associated with neurobiological abnormalities that have been observed in cocaine-dependent individuals (Volkow et al, 1993; Groman et al, 2011, 2020; Payer et al, 2014). Decision-making phenotypes could be used for assessing addiction risk in individuals prior to any drug exposure and, therefore, represent a potentially powerful approach for impeding the ongoing opioid epidemic.…”

Chronic Ethanol Exposure Produces Sex-Dependent Impairments in Value Computations in the Striatum

“…The ability to make flexible decisions is substantially altered by chronic ethanol (EtOH) use and dependence across species, impairing goal-directed behavior while enhancing habitual or stimulus-oriented behavior [1][2][3][4][5][6][7] . Low cognitive flexibility may contribute to future escalation of substance use [8][9][10] , including EtOH intake in both rodents and primates [11][12][13][14] , and in heightening the risk of relapse to alcohol use in humans 15,16 .…”

“…These findings highlight the profound impact of chronic EtOH exposure on adaptive decision-making, pinpointing specific changes in striatal representations of actions and outcomes as underlying mechanisms for cognitive deficits. 10 , including EtOH intake in both rodents and primates [11][12][13][14] and in heightening the risk of relapse to alcohol use in humans 15,16 .Cognitive flexibility, evaluated through reversal learning tasks 17,18 , involves learning beneficial choice and adapting to new action-outcome contingencies. Although the cognitive and neural mechanisms underlying chronic EtOH-induced reversal deficits are not yet fully understood, studies in humans have shown persistent disruption of reversal learning during protracted withdrawal from EtOH drinking [19][20][21][22] .…”