A double-blind placebo controlled experimental study of nicotine: I - effects on incentive motivation.

Rationale Brain reward pathways implicated in addiction appear to be less reactive in regular drug users; behavioural manifestations may include decreased sensitivity to natural reinforcers. Objectives This study aimed to replicate earlier findings of abstinence-associated incentive motivation deficits in smokers and to determine whether these can be reversed with nicotine in the form of lozenge. Methods One hundred forty-five smokers were each tested twice, once after receiving nicotine, and once after receiving placebo lozenge in counterbalanced order. Participants completed various tests of incentive motivational functioning: a measure of subjective enjoyment, the Snaith?Hamilton pleasure scale (SHAPS); a simple card sorting task, the card arranging reward responsivity objective test (CARROT) with and without financial incentive; the modified emotional Stroop test; a cue-reactivity task; and a novel reaction time task to explore effects of signals of reward, the incentive motivational enhancement of response speed task. Results Compared with performance during abstinence (placebo condition), nicotine was associated with: higher self-reported pleasure expectations on the SHAPS; enhanced responsiveness to financial reward on the CARROT in smokers who smoked 15 or more cigarettes a day; and greater interference from appetitive words on the Stroop task. Conclusions These results are generally consistent with contemporary neurobiological theories of addiction and suggest that short-term smoking abstinence is associated with impaired reward motivation which can be reversed with nicotine

NOP-related mechanisms in substance use disorders

Nociceptin/orphanin FQ (N/OFQ) is a 17 amino acid peptide that was deorphanized in 1995 and has been widely studied since. The role of the N/OFQ system in drug abuse has attracted researchers’ attention since its initial discovery. The first two scientific papers describing the effect of intracranial injection of N/OFQ appeared 20 years ago and reported efficacy of the peptide in attenuating alcohol intake, whereas heroin self-administration was insensitive. Since then more than 100 scientific articles investigating the role of the N/OFQ and N/OFQ receptor (NOP) system in drug abuse have been published. The present article provides an historical overview of the advances in the field with focus on three major elements. First, the most robust data supportive of the efficacy of NOP agonists in treating drug abuse come from studies in the field of alcohol research, followed by psychostimulant and opioid research. In contrast, activation of NOP appears to facilitate nicotine consumption. Second, emerging data challenge the assumption that activation of NOP is the most appropriate strategy to attenuate consumption of substances of abuse. This assumption is based first on the observation that animals carrying an overexpression of NOP system components are more prone to consume substances of abuse, whereas NOP knockout rats are less motivated to self-administer heroin, alcohol, and cocaine. Third, administration of NOP antagonists also reduces alcohol consumption. In addition, NOP blockade reduces nicotine self-administration. Hypothetical mechanisms explaining this apparent paradox are discussed. Finally, we focus on the possibility that co-activation of NOP and mu opioid (MOP) receptors is an alternative strategy, readily testable in the clinic, to reduce the consumption of psychostimulants, opiates, and, possibly, alcohol