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Paradoxical tolerance to cocaine after initial supersensitivity in drug-use-prone animals
Journal article   Open access   Peer reviewed

Paradoxical tolerance to cocaine after initial supersensitivity in drug-use-prone animals

Mark J Ferris, Erin S Calipari, James R Melchior, David C S Roberts, Rodrigo A España and Sara R Jones
The European journal of neuroscience, v 38(4), pp 2628-2636
Aug 2013
PMID: 23725404
url
https://doi.org/10.1111/ejn.12266View
Published, Version of Record (VoR) Open

Abstract

Dopamine Uptake Inhibitors - pharmacology Electrochemical Techniques Drug Tolerance Rats Male Rats, Sprague-Dawley Dopamine Uptake Inhibitors - administration & dosage Cocaine - administration & dosage Cocaine - pharmacology Exploratory Behavior - physiology Self Administration Animals Dopamine - metabolism
There is great interest in outlining biological factors and behavioral characteristics that either predispose or predict vulnerability to substance use disorders. Response to an inescapable novel environment has been shown to predict a "drug-use-prone" phenotype that is defined by rapid acquisition of cocaine self-administration. Here, we showed that response to novelty can also predict the neurochemical and behavioral effects of acute and repeated cocaine in rats. We used cocaine self-administration under a fixed-ratio 1 schedule followed by fast-scan cyclic voltammetry in brain slices to measure subsecond dopamine (DA) release and uptake parameters in drug-use-prone and -resistant phenotypes. Despite no significant differences in stimulated release and uptake, animals with high responses to a novel environment had DA transporters that were more sensitive to cocaine-induced uptake inhibition, which corresponded to greater locomotor activating effects of cocaine. These animals also acquired cocaine self-administration more rapidly and, after 5 days of extended access cocaine self-administration, high-responding animals showed robust tolerance to DA uptake inhibition by cocaine. The effects of cocaine remained unchanged in animals with low novelty responses. Similarly, the rate of acquisition was negatively correlated with DA uptake inhibition by cocaine after self-administration. Thus, we showed that tolerance to the cocaine-induced inhibition of DA uptake coexists with a behavioral phenotype that is defined by increased preoccupation with cocaine as measured by rapid acquisition and early high intake.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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