Prior exposure to salient win-paired cues in a rat gambling task increases sensitivity to cocaine self-administration and suppresses dopamine efflux in nucleus accumbens: support for the reward deficiency hypothesis of addiction (2019)

J Neurosci. 2019 Jan 9. pii: 3477-17. doi: 10.1523/JNEUROSCI.3477-17.2018.

Ferland JN1, Hynes TJ2, Hounjet CD2, Lindenbach D3, Vonder Haar C2, Adams WK2, Phillips AG3, Winstanley CA2.


Rats trained to perform a version of the rat gambling task (rGT) in which salient audiovisual cues accompany reward delivery, similar to commercial gambling products, show greater preference for risky options. Given previous demonstrations that probabilistic reinforcement schedules can enhance psychostimulant-induced increases in accumbal dopamine and locomotor activity, we theorised that performing this cued task could perpetuate a pro-addiction phenotype. Significantly more rats developed a preference for the risky options in the cued versus uncued rGT at baseline, and this bias was further exacerbated by cocaine self-administration, whereas the choice pattern of optimal decision-makers was unaffected. The addition of reward-paired cues therefore increased the proportion of rats exhibiting a maladaptive cognitive response to cocaine self-administration. Risky choice was not associated with responding for conditioned reinforcement or a marker of goal/sign-tracking, suggesting reward-concurrent cues precipitate maladaptive choice via a unique mechanism unrelated to simple approach towards, or responding for, conditioned stimuli. Although “protected” from any resulting decision-making impairment, optimal decision-makers trained on the cued rGT nevertheless self-administered more cocaine than those trained on the uncued task. Collectively, these data suggest repeated engagement with heavily-cued probabilistic reward schedules can drive addiction vulnerability through multiple behavioural mechanisms. Rats trained on the cued rGT also exhibited blunted locomotor sensitisation and lower basal accumbal dopamine levels, yet greater cocaine-induced increases in accumbal dopamine efflux. Gambling in the presence of salient cues may therefore result in an adaptive down regulation of the mesolimbic dopamine system, rendering individuals more sensitive to the deleterious effects of taking cocaine.

Significance statement

Impaired cost/benefit decision making, exemplified by preference for the risky, disadvantageous options on the Iowa Gambling Task (IGT), is associated with greater risk of relapse and treatment failure in substance use disorder. Understanding factors which enhance preference for risk may help elucidate the neurobiological mechanisms underlying maladaptive decision making in addiction, thereby improving treatment outcomes. Problem gambling is also highly comorbid with substance use disorder, and many commercial gambling products incorporate salient win-paired cues. Here we show that adding reward-concurrent cues to a rat analogue of the IGT precipitates a hypodopaminergic state, characterised by blunted accumbal dopamine efflux and attenuated locomotor sensitization, which may contribute to the enhanced responsivity to uncertain rewards or the reinforcing effects of cocaine we observed.

PMID: 30626700

DOI: 10.1523/JNEUROSCI.3477-17.2018