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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.
Behav Brain Res. 2014 Nov 01; 274:143-8.BB

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+Show Affiliations

Department of Psychology, Bloomsburg University of Pennsylvania, 400 E. 2nd St., Bloomsburg, PA 17815, USA. Electronic address: kball@bloomu.edu.Department of Psychology, Bloomsburg University of Pennsylvania, 400 E. 2nd St., Bloomsburg, PA 17815, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25127684

Citation

Ball, Kevin T., and Mylissa Slane. "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." Behavioural Brain Research, vol. 274, 2014, pp. 143-8.
Ball KT, Slane M. 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. Behav Brain Res. 2014;274:143-8.
Ball, K. T., & Slane, M. (2014). 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. Behavioural Brain Research, 274, 143-8. https://doi.org/10.1016/j.bbr.2014.08.010
Ball KT, Slane M. 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. Behav Brain Res. 2014 Nov 1;274:143-8. PubMed PMID: 25127684.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ball,Kevin T, AU - Slane,Mylissa, Y1 - 2014/08/12/ PY - 2014/03/08/received PY - 2014/07/04/revised PY - 2014/08/04/accepted PY - 2014/8/17/entrez PY - 2014/8/17/pubmed PY - 2015/5/27/medline KW - Cue KW - MDMA KW - Reinstatement KW - Self-administration KW - Sensitization KW - Tolerance SP - 143 EP - 8 JF - Behavioural brain research JO - Behav. Brain Res. VL - 274 N2 - 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/25127684/Tolerance_to_the_locomotor_activating_effects_of_34_methylenedioxymethamphetamine__MDMA__predicts_escalation_of_MDMA_self_administration_and_cue_induced_reinstatement_of_MDMA_seeking_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(14)00522-1 DB - PRIME DP - Unbound Medicine ER -