Prolactin suppression by (-) delta-9-tetrahydrocannabinol (THC): involvement of serotonergic and dopaminergic pathways.

(-) delta-9-Tetrahydrocannabinol (THC) was previously shown to suppress serum PRL levels (SPL) in rats. In the present study, various pathways by which THC suppresses PRL secretion were investigated. THC abolished the elevated SPL induced by either 5-hydroxytryptophan or melatonin. The SPL suppression after THC treatment was abolished upon treatment with cyproheptadine. These results suggest on involvement of a serotonergic pathway in the suppressive effect of THC on PRL secretion. Elevated SPL induced by a low dose of the dopaminergic blocker pimozide was suppressed after treatment with THC. However, elevated SPL, induced by a high dose of pimozide or by any dose of perphenazine (a less specific dopaminergic blocker), were not reduced by combined treatment of either of these drugs with THC. It seems that THC also enhances the dopaminergic activity in the pathway that controls PRL secretion. In addition, the pimozide-induced SPL elevation dropped upon combined treatment of cyproheptadine and pimozide. As cyproheptadine alone, and in the dose used, did not affect SPL, it is proposed that the serotonergic and dopaminergic pathways that control PRL secretion do not necessarily act independently of one another.