Dissociable effects of cocaine and yohimbine on impulsive action and relapse to cocaine seeking

Abstract

RationaleA strong association has been demonstrated between various forms of impulsivity and addiction-like behavior in both humans and rats.ObjectivesIn this study, we investigated how impulsive action, as measured in the 5-choice serial reaction time task (5-CSRTT), is affected during various stages of cocaine taking and seeking and by relapse-provoking stimuli in animals that were trained both in an intravenous cocaine self-administration paradigm and in the 5-CSRTT.MethodsRats were concurrently trained in the 5-CSRTT and cocaine self-administration protocol, and subsequently, the effects of cocaine (7.5 mg/kg) and the pharmacological stressor yohimbine (1.25 mg/kg) were tested in both paradigms.ResultsCocaine self-administration (5 h/day) transiently altered impulsive action and increased errors of omission in the 5-CSRTT. Pharmacological challenges with cocaine and yohimbine induced increments in impulsive action and reinstated cocaine-seeking responses within the same animals. Further analyses revealed that the effects of cocaine and yohimbine on impulsive action did not correlate with their effects on reinstatement of cocaine seeking.ConclusionsThese data suggest that although impulsive action and relapse can be pharmacologically modulated in the same direction within individuals, these effects appear not to be directly coupled.

Kappa opioid receptors mediate yohimbine-induced increases in impulsivity in the 5-choice serial reaction time task

“…To our knowledge, only one study has examined the relationship between yohimbine-induced increases in impulsivity and yohimbine-induced reinstatement. In this study, yohimbine-induced reinstatement of cocaine seeking was not significantly correlated with the increased premature responding in the 5-CSRTT [22]. However, these correlational results do not completely rule out a role for impulsivity in the effects of yohimbine on reinstatement, because yohimbine increases both motor [23,42] and choice impulsivity [64].…”

“…Delay tasks are thought to measure impulsive choice, whereas stop-signal tasks index motor impulsivity, the ability to inhibit motor responses [48]. The type of impulsivity indexed by the 5-CSRTT has been suggested to overlap with that of delay and stop-signal tasks [22,48]. Examination of multiple paradigms may be necessary to determine the effects of a given drug on impulsivity.…”

“…Impulsivity may be a predisposing factor in acquisition of drug self-administration has also been linked to reinstatement [18][19][20][21]. The pharmacological stressor yohimbine reinstates drug-seeking and also increases impulsivity in the 5-choice serial reaction time task (5-CSRTT) [22,23]. We showed that the KOR antagonist nor-binaltorphimine (nor-BNI) blocks yohimbineinduced reinstatement of alcohol and nicotine seeking [7,8].…”

Brain and Cognition for Addiction Medicine: From Prevention to Recovery Neural Substrates for Treatment of Psychostimulant-Induced Cognitive Deficits

“…However, it is not known if repeated use of drugs of abuse induces impulsivity in humans. In animals, repeated administration of cocaine, methamphetamine, and nicotine increased impulsive behavior in animals (39–43). This increase in impulsivity was observed both when animals were challenged with the drug of abuse and during withdrawal from the drug (i.e., when animals were not under the influence of the drug).…”

Assessing Impulsivity in Humans and Rodents: Taking the Translational Road

“…Rodent task validation, on the other hand, is partially assumed by the similarities to their human counterparts, as most of these contexts can only be partially replicated in rodents. However, all the here-described rodent tasks have shown alterations of impulsivity associated with substances of abuse (e.g., 5-csrtt, Broos et al, 2017;5C-CPT, Irimia et al, 2014;SST, Beckwith and Czachowski, 2016;DD, Harvey-Lewis et al, 2014;and VDS, Leite-Almeida et al, 2013).…”