The role of impulsivity in the aetiology of drug dependence: reward sensitivity versus automaticity

Journal ArticleResearch Support, Non-U.S. Gov'tCopyright © The Author(s) 2011.RATIONALE: Impulsivity has long been known as a risk factor for drug dependence, but the mechanisms underpinning this association are unclear. Impulsivity may confer hypersensitivity to drug reinforcement which establishes higher rates of instrumental drug-seeking and drug-taking behaviour, or may confer a propensity for automatic (non-intentional) control over drug-seeking/taking and thus intransigence to clinical intervention. METHOD: The current study sought to distinguish these two accounts by measuring Barratt Impulsivity and craving to smoke in 100 smokers prior to their completion of an instrumental concurrent choice task for tobacco (to measure the rate of drug-seeking) and an ad libitum smoking test (to measure the rate of drug-taking-number of puffs consumed). RESULTS: The results showed that impulsivity was not associated with higher rates of drug-seeking/taking, but individual differences in smoking uptake and craving were. Rather, nonplanning impulsivity moderated (decreased) the relationship between craving and drug-taking, but not drug-seeking. CONCLUSIONS: These data suggest that whereas the uptake of drug use is mediated by hypervaluation of the drug as an instrumental goal, the orthogonal trait nonplanning impulsivity confers a propensity for automatic control over well-practiced drug-taking behaviour.MR

Pharmacology of MDMA- and Amphetamine-Like New Psychoactive Substances

New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran basic chemical structures have recently emerged for recreational drug use. Detailed information about their psychotropic effects and health risks is often limited. At the same time, it emerged that the pharmacological profiles of these NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine (NE) and dopamine (DA) transporter (NET and DAT) inhibition and transporter-mediated release of NE and DA, thus showing a more catecholamine-selective profile. MDMA-like NPS frequently induce well-being, empathy, and prosocial effects and have only moderate psychostimulant properties. These MDMA-like substances primarily act by inhibiting the serotonin (5-HT) transporter (SERT) and NET, also inducing 5-HT and NE release. Monoamine receptor interactions vary considerably among amphetamine- and MDMA-like NPS. Clinically, amphetamine- and MDMA-like NPS can induce sympathomimetic toxicity. The aim of this chapter is to review the state of knowledge regarding these substances with a focus on the description of the in vitro pharmacology of selected amphetamine- and MDMA-like NPS. In addition, it is aimed to provide links between pharmacological profiles and in vivo effects and toxicity, which leads to the conclusion that abuse liability for amphetamine-like NPS may be higher than for MDMA-like NPS, but that the risk for developing the life-threatening serotonin syndrome may be increased for MDMA-like NPS