Nociceptin stimulates locomotion and exploratory behaviour in mice

Eur J Pharmacol. 1996 Dec 12;317(1):9-13. doi: 10.1016/s0014-2999(96)00707-8.


The recently characterized heptadecapeptide nociceptin, the endogenous agonist of the orphan opioid receptor-like 1 (ORL1 receptor), has been tested for its effects on locomotion and exploratory behaviour in mice. I.c.v. administration of as little as 10 ng of nociceptin/animal stimulated locomotor activity. This effect was dose-dependent, increasing in intensity up to 100 ng and in duration for doses in the range of 1000-10000 ng. The stimulation of horizontal locomotion elicited by 100 ng nociceptin was accompanied by a stimulation of the vertical component of locomotion. These effects were not reversed by high doses (1.5 and 4.5 mg/kg s.c.) of the opioid receptor antagonist naloxone. Increasing doses of the dopamine D2 receptor antagonist haloperidol (0.1-0.5 mg/kg i.p.) as well as of the dopamine D1 receptor antagonist SCH 23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride] (0.0075-0.03 mg/kg s.c.) reversed this effect, suggesting that nociceptin exerts its motor-stimulant actions by increasing central dopaminergic transmission. Nociceptin was also found to increase the number of head dips in the hole-board test, indicating that the peptide stimulates exploratory behaviour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects*
  • Haloperidol / pharmacology
  • Injections, Intraventricular
  • Male
  • Mice
  • Motor Activity / drug effects*
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Opioid Peptides / administration & dosage
  • Opioid Peptides / antagonists & inhibitors
  • Opioid Peptides / pharmacology*
  • Receptors, Opioid / agonists*
  • Stimulation, Chemical


  • Benzazepines
  • Dopamine Antagonists
  • Narcotic Antagonists
  • Opioid Peptides
  • Receptors, Opioid
  • Naloxone
  • nociceptin
  • nociceptin receptor
  • Haloperidol