Journal article
Paradoxical tolerance to cocaine after initial supersensitivity in drug-use-prone animals
The European journal of neuroscience, v 38(4), pp 2628-2636
Aug 2013
PMID: 23725404
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Paradoxical tolerance to cocaine after initial supersensitivity in drug-use-prone animals
- Creators
- Mark J Ferris - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USAErin S CalipariJames R MelchiorDavid C S RobertsRodrigo A EspañaSara R Jones
- Publication Details
- The European journal of neuroscience, v 38(4), pp 2628-2636
- Publisher
- Wiley; France
- Grant note
- R01 DA024095 / NIDA NIH HHS F31 DA031533 / NIDA NIH HHS R01 DA14030 / NIDA NIH HHS P50 DA006634 / NIDA NIH HHS T32 DA007246 / NIDA NIH HHS R01 DA021325 / NIDA NIH HHS R01 DA030161 / NIDA NIH HHS R01 DA014030 / NIDA NIH HHS K99 DA031791 / NIDA NIH HHS K01 DA025279 / NIDA NIH HHS R01 DA03016 / NIDA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000323195100013
- Scopus ID
- 2-s2.0-84882619341
- Other Identifier
- 991014877717004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences