Behavioral sensitization to heroin by cannabinoid pretreatment in the rat

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.