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Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long- but not short-access rats

Academic Article
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Overview

authors

  • Greenwell, T. N.
  • Funk, C. K.
  • Cottone, P.
  • Richardson, H. N.
  • Chen, S. A.
  • Rice, K. C.
  • Zorrilla, Eric
  • Koob, George

publication date

  • April 2009

journal

  • Addiction Biology  Journal

abstract

  • Dysregulation of the stress-related corticotropin-releasing factor (CRF) system has been implicated in the development of drug dependence. The present study examined the effects of administering CRF type 1 (CRF(1)) receptor antagonists on heroin self-administration in animals allowed short (1 hour) or long (8-12 hours) access to intravenous heroin self-administration sessions. The nonpeptide CRF(1) antagonists MJL-1-109-2 (1 hour versus 8 hours access) or R121919 (1 hour versus 12 hours access) were systemically injected in both short- and long-access rats. MJL-1-109-2 (10 mg/kg) and R121919 (10 and 20 mg/kg) reduced heroin self-administration in long-access animals without altering heroin intake in short-access animals. Both MJL-1-109-2 and R121919 decreased first-hour intravenous heroin self-administration selectively in long-access rats, with R121919 decreasing cumulative heroin intake across the 12-hour session. The results demonstrate that blockade of the CRF-CRF(1) receptor system attenuates the increased heroin intake of rats with extended access to the drug.

subject areas

  • Animals
  • Blood-Brain Barrier
  • Feeding Behavior
  • Heroin Dependence
  • Male
  • Pyrimidines
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone
  • Self Administration
  • Time Factors
  • Triazines
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Research

keywords

  • Addiction
  • CRF
  • antagonist
  • escalation
  • heroin
  • self-administration
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Identity

PubMed Central ID

  • PMC2748834

International Standard Serial Number (ISSN)

  • 1355-6215

Digital Object Identifier (DOI)

  • 10.1111/j.1369-1600.2008.00142.x

PubMed ID

  • 19291009
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Additional Document Info

start page

  • 130

end page

  • 143

volume

  • 14

issue

  • 2

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