Dissociation between behavioral effects and changes in metabolism of cerebral serotonin following δ⁹-tetrahydrocannabinol

Abstract

Behavioral changes, reaction times in analgesic tests and effects on metabolism of cerebral serotonin (5 HT) were monitored in male Sprague-Dawley rats following the administration ofδ ⁹-tetrahydrocannabinol (THC) as a propylene glycol-serum complex. THC (5.5 mg/kg i.p. and 1.0 mg/kg i.v.) produced characteristic and reproducible behavioral effects, including catalepsy and squealing, as well as significant increases in the reaction time as determined in both the hot plate and tail flick tests for analgesia. Intraventricular injection of THC caused many of the changes seen after systemic administration of the drug. The levels of 5 HT and its principle metabolite, 5-hydroxyindoleacetic acid (5 HIAA) were measured in forebrain and brainstem following THC. No significant change in the level of either indole was observed. Moreover, THC did not alter the turnover of cerebral 5 HT as determined by the probenecid method and did not change the increase in 5 HT following the administration of pargyline. It may thus be concluded that doses of THC which produce significant and reproducible behavioral modifications do not alter the dynamics of the cerebral serotonergic system.