Behavioral sensitization to heroin by cannabinoid pretreatment in the rat

The behavioral consequences of acute heroin challenge (0.5 mg/kg;g, s.c.) w ere measured in rats previously submitted to repeated administration of inc reasing doses of the synthetic cannabinoid receptor agonist, R(+)-[2,3-dihy dro-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 d ay 4 mg/kg, third day 8 mg/kg) or vehicle. Heroin administration to rats pr etreated with vehicle produced catalepsy. The same dose of heroin in WIN552 12.2-pretreated rats was followed by a marked increase of locomotor activit y with stereotyped and non-stereotyped behaviors. These effects were blocke d by the opioid receptor antagonist, naloxone. These Endings indicate that pretreatment with WIN55212.2 produces cross-sensitization to heroin in the rat. These changes might reflect long-lasting changes of receptor populatio n or transcriptional mechanisms in the mesolimbic system. (C) 2001 Publishe d by Elsevier Science B.V.