Psychopharmacology

, Volume 164, Issue 2, pp 168–176

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

  • Kabirullah Lutfy
  • Imran Khaliq
  • Ivy F. Carroll
  • Nigel T. Maidment
Original Investigation

DOI: 10.1007/s00213-002-1192-1

Cite this article as:
Lutfy, K., Khaliq, I., Carroll, I.F. et al. Psychopharmacology (2002) 164: 168. doi:10.1007/s00213-002-1192-1

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.

Orphanin FQ/nociceptin Cocaine J-113397 Ventral tegmental area Motor activity Sensitization

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Kabirullah Lutfy
    • 1
  • Imran Khaliq
    • 1
  • Ivy F. Carroll
    • 2
  • Nigel T. Maidment
    • 1
  1. 1.Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024, USA
  2. 2.Research Triangle Institute, Research Triangle Park, NC 27709, USA