Biology subjects

Ahmed, S. H.

Publications and source records attributed to Ahmed, S. H..

3 recordsLinked to original sources

bioRxiv2020

Probing the decision-making mechanisms underlying choice between drug and nondrug rewards in rats

Investigating the decision-making mechanisms underlying choice between drug and nondrug rewards is essential to understand how their alterations can contribute to substance use disorders. However, despite some recent effort, this investigation remains a challenge in a drug choice setting, notably when it comes to delineate the role of goal-directed versus habitual control mechanisms. The goal of this study was to try probing these different mechanisms by comparing response latencies measured during sampling (i.e., only one option is available) and choice trials. A deliberative goal-directed control mechanism predicts a lengthening of latencies during choice whereas a habitual control mechanism predicts no change in latencies. Alternatively, a race-like response competition mechanism, such as that postulated by the behavioral ecology-inspired Sequential Choice Model (SCM), predicts instead a shortening of response latencies during choice compared to sampling. Here we tested the predictions of these different mechanisms by conducting a systematic retrospective analysis of all cocaine versus saccharin choice experiments conducted in rats in our laboratory over the past 12 years. Overall, we found that rats engage a deliberative goal-directed mechanism after limited training, but shift to a SCM-like response selection mechanism after more extended training. The latter finding suggests that habitual control is engaged in a choice setting via a race-like response competition mechanism, and thus, that the SCM is not a general model of choice, as formulated initially, but a specific model of habitual choice.

animal behavior and cognition↗

bioRxiv2020

Loss of resistance to punishment of cocaine use after prior experience

One behavioral feature of drug addiction is continued drug use despite awareness that this causes negative consequences. Attempts to model this feature in animals typically involve punishing drug self-administration with a brief electrical footshock and look for resistance to punishment. Though all individual animals eventually stop self-administering the drug with increasing intensity of punishment, some individuals do so at higher intensities than other individuals. The greater relative resistance to punishment of the former individuals is generally interpreted as evidence for a compulsion-like behavior. Here we show that resistance to footshock punishment is in fact not a stable individual behavioral feature. Specifically, when rats are retested for their resistance to increasing intensity of footshock punishment, they become much less resistant. As a result, they suppress their cocaine intake even when punished with an initially low and ineffective intensity. A series of original behavioral experiments reveals that this low resistance to footshock punishment is rapidly acquired after rats experience a punishment intensity that leads them to near-completely suppress their cocaine intake. Passive exposure to the same intensity does not induce this effect. Once acquired, low resistance to punishment persists during at least one month, but can nevertheless be extinguished by retesting rats on a daily basis. Interestingly, this acquired low resistance to footshock punishment does not generalize to a non-painful form of punishment (i.e., histamine) that is also seldom used in animal drug self-administration studies. We discuss some possible theoretical and methodological implications of these findings for future research on animal models of compulsion-like behavior.

neuroscience↗

bioRxiv2020

Pharmacokinetics trumps pharmacodynamics during cocaine choice: a reconciliation with the dopamine hypothesis of addiction

Cocaine is known to increase brain dopamine at supranormal levels in comparison to alternative nondrug rewards. According to the dopamine hypothesis of addiction, this difference would explain, at least in part, why the latter are eventually given up in favor of continued cocaine use during the transition to addiction. Though resting on solid neuroscientific foundations, this hypothesis has nevertheless proven difficult to reconcile with research on cocaine choice in experimental animals. When facing a choice between an intravenous bolus of cocaine and a nondrug alternative (e.g., sweet water), both delivered immediately after choice, rats do not choose the drug, as would be predicted, but instead develop a strong preference for the nondrug alternative, sometimes to the exclusion of continued drug use. Here we report converging evidence that reconciles this finding with the dopamine hypothesis of addiction. Briefly, our data suggest that cocaine is indeed supranormal in reward magnitude, as postulated by the dopamine hypothesis of addiction, but is less preferred during choice because its pharmacokinetics makes it an inherently more delayed reward than the alternative. Reframing previous drug choice studies in rats as intertemporal choice studies reveals that the discounting effects of delays spare no rewards, including supranormal ones, and that during choice, pharmacokinetics trumps pharmacodynamics. Finally, this study also reveals important gaps in our understanding of drug reward delays that need to be filled by future experimental and theoretical work.

neuroscience↗