| Self-Administration of Cocaine Induces Dopamine-Independent Self-Administration of Sigma Agonists. | |
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MedLine Citation:
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PMID: 23187725 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Sigma(1) receptors (σ(1)Rs) are intracellularly mobile chaperone proteins implicated in several disease processes, as well as psychiatric disorders and substance abuse. Here we report that although selective σ(1)R agonists (PRE-084, (+)-pentazocine) lacked reinforcing effects in drug-naive rats, over the course of 28 experimental sessions, which was more than sufficient for acquisition of cocaine self-administration, responding was not maintained by either σ(1)R agonist. In contrast, after subjects self-administered cocaine σ(1)R agonists were readily self-administered. The induced reinforcing effects were long lasting; a response for which subjects had no history of reinforcement was newly conditioned with both σ(1)R agonists, extinguished when injections were discontinued, and reconditioned when σ(1)R agonists again followed responses. Experience with food reinforcement was ineffective as an inducer of σ(1)R agonist reinforcement. Although a variety of dopamine receptor antagonists blocked cocaine self-administration, consistent with its dopaminergic mechanism, PRE-084 self-administration was entirely insensitive to these drugs. Conversely, the σR antagonist, BD1063, blocked PRE-084 self-administration but was inactive against cocaine. In microdialysis studies i.v. PRE-084 did not significantly stimulate dopamine at doses that were self-administered in rats either with or without a cocaine self-administration experience. The results indicate that cocaine experience induces reinforcing effects of previously inactive σ(1)R agonists, and that the mechanism underlying these reinforcing effects is dopamine independent. It is further suggested that induced σ(1)R mechanisms may have an essential role in treatment-resistant stimulant abuse, suggesting new approaches for the development of effective medications for stimulant abuse.Neuropsychopharmacology (2012) 0, 000-000. advance online publication, 28 November 2012; doi:10.1038/npp.2012.224. |
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Authors:
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Takato Hiranita; Maddalena Mereu; Paul L Soto; Gianluigi Tanda; Jonathan L Katz |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-28 |
Journal Detail:
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Title: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Volume: - ISSN: 1740-634X ISO Abbreviation: Neuropsychopharmacology Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8904907 Medline TA: Neuropsychopharmacology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Psychobiology Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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