Differential vulnerability to the punishment of cocaine related behaviours: effects of locus of punishment, cocaine taking history and alternative reinforcer availability

Abstract

BackgroundThe availability of alternative reinforcement has been shown to reduce drug use, but it remains unclear whether it facilitates a reduction or cessation of drug seeking or taking.ObjectivesWe compared the effects of punishment of cocaine seeking or taking behaviour after brief or extended cocaine-taking histories when behavioural reallocation was facilitated or not by making available an alternative ingestive reinforcer (sucrose).MethodsIn the first experiment, punishment of either seeking or taking responses was introduced immediately after training on the seeking-taking chained schedule. In the second experiment, punishment of cocaine seeking was introduced after 12 additional days of either 1 or 6 h daily access to cocaine self-administration. In both experiments, beginning 1 week before the introduction of punishment, a subset of rats had concurrent nose poke access to sucrose while seeking or taking cocaine.ResultsThe presence of an alternative source of reinforcement markedly facilitated behavioural reallocation from punished cocaine taking after acquisition. It also facilitated punishment-induced suppression of cocaine seeking after an extensive cocaine self-administration history likely by prompting goal-directed motivational control over drug use. However, a significant proportion of rats were deemed compulsive—maintaining drug use after an extensive cocaine history despite the presence of abstinence-promoting positive and negative incentives.ConclusionMaking available an alternative reinforcer facilitates disengagement from punished cocaine use through at least two different processes but remains ineffective in a subpopulation of vulnerable animals, which continued to seek cocaine despite the aversive consequence of punishment and the presence of the alternative positive reinforcer.

Genome-wide DNA hydroxymethylation identifies potassium channels in the nucleus accumbens as discriminators of methamphetamine addiction and abstinence

“…27 In order to investigate epigenetic dysfunctions that may subsume METH addiction, we used a model of compulsive drug taking that was recently shown to produce a subgroup of rats that continue to lever press compulsively for cocaine despite adverse consequences. [28][29][30] Here, we show that there also exists a subpopulation of rats that continue to lever press for METH even in the presence of footshocks, whereas other rats became progressively more abstinent with increasing shock intensity. Moreover, we discovered that rats that differ phenotypically also exhibited substantial differences in DNA hydroxymethylation in peaks located near or within genes that are relevant to synaptic plasticity and cognition.…”

“…41 The recent development of animal models that better mimic drug addiction in rodents 29,30,42 should help to improve the characterization of cellular and molecular substrates …”

A single alcohol drinking session is sufficient to enable subsequent aversion-resistant consumption in mice

“…Several studies of aversion-resistant intake for cocaine and alcohol suggest that there may be two populations of animals, one that is aversion-resistant and one that is aversion-sensitive (Cooper et al, 2007, Deroche-Gamonet et al, 2004 and Pelloux et al, 2015; see Discussion section). Thus, we examined the distribution of drinking levels in these larger cohorts of mice drinking data, and used a Kruskal–Wallis test to assess whether the distributions deviated significantly from a normal distribution.…”

Alcohol use disorder symptoms are associated with greater relative value ascribed to alcohol, but not greater discounting of costs imposed on alcohol

“…reduced prediction error coding, cognitive inflexibility, task disengagement), rather than a specific deficit in punishment sensitivity. Finally, insensitivity to the suppressive effects of shock on drug self-administration found in impulsive or extended drug access rats may not reflect cost discounting per se, but rather, may reflect greater value ascribed to the drug which was not effectively assessed by the single lever self-administration procedures used in previous studies (Bentzley et al 2014; Pelloux et al 2015). Altogether, this analysis and the current data weaken support for the claim that human drug dependence is driven by discounting costs associated with drug use.…”

“…Third, drug users show deficits in reversal learning which could be driven by insensitivity to punishment of the incorrect response during reversal (Ersche et al 2008; Fortier et al 2008; Reiter et al 2016; Vanes et al 2014). Finally, rats that are impulsive or have had extended access to the drug are less sensitive than control rats to the suppression of drug self-administration by contingent shock punishment, despite comparable baseline self-administration rates, suggesting equivalent drug valuation and selective discounting of costs (Belin et al 2008; Economidou et al 2009; Pelloux et al 2007; Pelloux et al 2015; Vanderschuren and Everitt 2004). …”