title: Tolerance to the locomotor-activating effects of 3,4-methylenedioxymethamphetamine (MDMA) predicts escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking in rats.
abstract: Pre-clinical studies of individual differences in addiction vulnerability have been increasing over recent years, but the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) has received relatively little attention in this regard. Previously, we reported large individual differences both in rats' initial behavioral response to experimenter-administered MDMA and their degree of behavioral sensitization to repeated administration. To determine whether these differences could predict subsequent patterns of MDMA-taking or -seeking behaviors we used the self-administration-extinction-reinstatement model to examine addiction-like behavior (i.e., escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking) in rats a priori characterized for either locomotor sensitization or tolerance to MDMA. Rats that developed tolerance to the locomotor-activating effects of MDMA had a significantly larger locomotor response to the first MDMA injection relative to rats that developed sensitization. Importantly, rats that developed tolerance subsequently displayed an escalation of MDMA self-administration over days, as well as clear cue-induced reinstatement of MDMA seeking following extinction. Conversely, rats that developed locomotor sensitization to MDMA subsequently maintained relatively stable levels of MDMA self-administration over days and showed no cue-induced reinstatement of MDMA seeking. These results show that differences in the level of psychomotor activation following acute and repeated MDMA administration can reliably predict two important addiction-like behaviors in rats, which may have implications in the prediction of compulsive MDMA use in humans.
authors.affiliation: Department of Psychology, Bloomsburg University of Pennsylvania, 400 E. 2nd St., Bloomsburg, PA 17815, USA. Electronic address: kball@bloomu.edu.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Ball
authors.affiliation: Department of Psychology, Bloomsburg University of Pennsylvania, 400 E. 2nd St., Bloomsburg, PA 17815, USA.
authors.forename: Mylissa
authors.initials: M
authors.lastname: Slane
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D006120:Grooming / Q000187:drug effects; D006213:Hallucinogens / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: Cue; MDMA; Reinstatement; Self-administration; Sensitization; Tolerance