Orphanin FQ/nociceptin blocks cocaine-induced behavioral sensitization in rats

Psychopharmacology (Berl). 2002 Nov;164(2):168-76. doi: 10.1007/s00213-002-1192-1. Epub 2002 Aug 30.

Abstract

Rationale: Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL-1) receptor, shows similarities to dynorphin A (1-17) in structure and functions. Dynorphin and other kappa opioid receptor agonists have been shown to block cocaine sensitization.

Objective: The present study was designed to examine the ability of OFQ/N to block cocaine-induced behavioral sensitization.

Methods: Rats were habituated to testing chambers for 1 h, injected with artificial cerebrospinal fluid (aCSF) or OFQ/N (15 nmol) followed by saline or cocaine (20 mg/kg) and locomotor activity was measured for a further 1 h. Rats were treated similarly for the next 2 days except the dose of OFQ/N was doubled on each subsequent day. Rats were then challenged with cocaine (7.5 mg/kg) in the absence of OFQ/N on day 8. The specificity of OFQ/N's action was examined in the presence of J-113397 (30 nmol), an ORL-1 receptor antagonist. The ability of OFQ/N to block the context-independent component of cocaine sensitization was also tested wherein rats were treated in their home cages on days 1-3. Finally, the effect of intra-VTA OFQ/N administration on cocaine sensitization was examined.

Results: Sensitization did not develop in rats repeatedly treated with OFQ/N, via either route of administration, prior to cocaine administration on days 1-3. The inhibitory effect of OFQ/N was not dependent on context and was blocked by pretreatment with J-113397.

Conclusion: Our results indicate that OFQ/N blocks cocaine-induced behavioral sensitization through activation of the ORL-1 receptor and that the VTA may be one of the substrates for this action of OFQ/N.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzimidazoles / pharmacology
  • Cocaine / administration & dosage
  • Cocaine / antagonists & inhibitors
  • Cocaine / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Tolerance
  • Injections, Intraventricular
  • Locomotion / drug effects*
  • Locomotion / physiology
  • Male
  • Narcotic Antagonists
  • Opioid Peptides / administration & dosage
  • Opioid Peptides / pharmacology*
  • Piperidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid
  • Time Factors
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology

Substances

  • Benzimidazoles
  • J 113397
  • Narcotic Antagonists
  • Opioid Peptides
  • Piperidines
  • Receptors, Opioid
  • nociceptin
  • nociceptin receptor
  • Cocaine