Abstract
RationaleLong-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known.ObjectiveIn this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype.MethodsA double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic reversal learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based reversal learning.ResultsProportion correct on the reversal learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on reversal learning.ConclusionsThese data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-015-4141-5) contains supplementary material, which is available to authorized users.
Highlights
Reversal learning is the ability to flexibly adapt behavior in response to changing stimulus–outcome contingencies
These data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning
We investigated the acute effects of cannabis and cocaine in healthy regular users of these drugs
Summary
Reversal learning is the ability to flexibly adapt behavior in response to changing stimulus–outcome contingencies. Impaired reversal learning is a dimension of impulsivity-related traits. Trait impulsivity, which includes reversal learning, has been related to enhanced drug self-administration levels in rodents (Cervantes et al 2013; Izquierdo and Jentsch 2012; Dalley et al 2007). How acute effects of drugs of abuse causally affect reversal learning in humans is yet to be established. For cocaine, acute effects are often fundamentally different from chronic use. Long-term studies often show impairments on cognitive functions, while acute administration most often yields cognitive enhancing effects (Fillmore et al 2006; Garavan et al 2008; Spronk et al 2013, 2015). We examined reversal learning following the acute administration of cannabis and cocaine, the two most commonly used illicit drugs in Europe (EMCDDA 2014). We investigated drug-induced effects on reversal learning as a function of genetic variants in two common dopaminergic candidate genes
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