Behavioral sensitization to heroin by cannabinoid pretreatment in the rat

Eur J Pharmacol. 2001 Jun 15;421(3):R1-3. doi: 10.1016/s0014-2999(01)01056-1.


The behavioral consequences of acute heroin challenge (0.5 mg/kg, s.c.) were measured in rats previously submitted to repeated administration of increasing doses of the synthetic cannabinoid receptor agonist, R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55212.2) (first day 2 mg/kg, second day 4 mg/kg, third day 8 mg/kg) or vehicle. Heroin administration to rats pretreated with vehicle produced catalepsy. The same dose of heroin in WIN55212.2-pretreated rats was followed by a marked increase of locomotor activity with stereotyped and non-stereotyped behaviors. These effects were blocked by the opioid receptor antagonist, naloxone. These findings indicate that pretreatment with WIN55212.2 produces cross-sensitization to heroin in the rat. These changes might reflect long-lasting changes of receptor population or transcriptional mechanisms in the mesolimbic system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Behavior, Animal / drug effects*
  • Benzoxazines
  • Cannabinoids / metabolism
  • Cannabinoids / pharmacology*
  • Dose-Response Relationship, Drug
  • Heroin / pharmacology*
  • Male
  • Morpholines / pharmacology*
  • Motor Activity / drug effects
  • Naphthalenes / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists


  • Analgesics
  • Benzoxazines
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • Receptors, Cannabinoid
  • Receptors, Drug
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Heroin