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

Addict Biol. 2009 Apr;14(2):130-43. doi: 10.1111/j.1369-1600.2008.00142.x.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Feeding Behavior / drug effects
  • Heroin Dependence / prevention & control*
  • Male
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Self Administration
  • Time Factors
  • Triazines / administration & dosage
  • Triazines / pharmacology*


  • MJL 1-109-2
  • Pyrimidines
  • R 121919
  • Receptors, Corticotropin-Releasing Hormone
  • Triazines
  • CRF receptor type 1