Contribution of impulsivity and novelty-seeking to the acquisition and maintenance of MDMA self-administration

Impulsivity, but not novelty-seeking, predicts how strongly rats seek MDMA after withdrawal. Before self-administration, rats were tested for impulsivity (premature responding on a five-choice task) and novelty-seeking (locomotor activity in a novel environment). Impulsivity was positively correlated with the magnitude of drug-seeking triggered by MDMA, while novelty-seeking showed no significant link to either acquisition or drug-seeking. MDMA self-administration also caused transient deficits in attention and increased premature responses. The findings suggest impulsivity may be a risk factor for compulsive drug-seeking after MDMA withdrawal.

Study at a glance

Abstract

It has been suggested that the response to novelty and impulsivity predict the latency to acquisition and maintenance of drug self-administration, respectively. The aim of this study was to examine the relationship between these two traits and (1) the latency to acquisition and (2) maintenance (drug-seeking) of 3,4-methylenedioxymethamphetamine (MDMA) self -administration. Impulsivity, measured as premature responding on the five-choice serial reaction time task (5-CSRTT), and novelty-seeking, measured as the locomotor response in a novel environment, were measured prior to self-administration. Latency to acquisition was determined as the number of test sessions required to self-administer an initial criterion of 90 infusions of 1.0 mg/kg/infusion, as well as an additional 150 infusions of 0.5 mg/kg/infusion MDMA. For some rats, the ability of MDMA [0, 5.0 or 10.0 mg/kg, intraperitoneal (IP)] to produce drug-seeking was subsequently measured, and for others, impulsivity was again measured following self-administration. Novelty-seeking was not significantly correlated with either the acquisition or drug-seeking measures of MDMA self-administration. Impulsivity was not significantly correlated with the latency to acquire self-administration of MDMA, but was significantly and positively correlated with the magnitude of MDMA-produced drug-seeking. Furthermore, MDMA self-administration produced a number of notable, but transient, deficits in the 5-CSRTT; there was an increase in omission rate and a delayed increase in premature responses in particular. These findings suggest that impulsivity, but not sensation seeking, might be a risk factor for the development of compulsive drug-seeking following withdrawal from MDMA self-administration.