ACUTE EFFECTS OF DELTA(9)-TETRAHYDROCANNABINOL ON TUBEROINFUNDIBULAR DOPAMINE ACTIVITY, ANTERIOR-PITUITARY SENSITIVITY TO DOPAMINE AND PROLACTIN-RELEASE VARY AS A FUNCTION OF ESTROUS-CYCLE

The effects of Delta(9)-tetrahydrocannabinol (THC) on the activity of brain dopaminergic neurons might be subject to gonadal influence. In t his work, we tested this hypothesis in relation to the effects of THC on tuberoinfundibular dopaminergic (TIDA) activity, the anterior pitui tary sensitivity to dopamine (DA) and prolactin (PRL) secretion. To th is end, we examined the effects of an acute dose of this cannabinoid a dministered during different phases of the estrous cycle in the mornin g or afternoon. The results were as follows. THC, administered during the morning of estrus, stimulated TIDA activity as reflected by increa ses in DA and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents and ty rosine hydroxylase (TH) activity in the medial basal hypothalamus. Thi s was accompanied by an increase in the responsiveness of the anterior pituitary to DA, as reflected by the increase in the density of D-2 r eceptors and the corresponding decrease in PRL release. By contrast, p lasma PRL levels increased when THC was administered on the afternoon of estrus, in parallel with a significant reduction in the number of D -2 receptors in the anterior pituitary gland and no effects on TIDA ac tivity. A similar decrease in the anterior pituitary density of D-2 re ceptors, but with no changes in plasma PRL levels, was observed when T HC was administered during the morning of diestrus. This effect was no t accompanied by changes in TIDA activity either. The administration o f THC during the afternoon of diestrus stimulated TIDA activity (incre ases in DA and DOPAC contents and TH activity in the medial basal hypo thalamus), as occurred when the cannabinoid was administered during th e morning of estrus, but in this case, it decreased the density of D-2 receptors in the anterior pituitary and did not modify plasma PRL lev els. These results contrast with the absence of significant changes ob served when THC was administered during the morning or the afternoon o f proestrus, although the highest plasma PRL levels and TIDA activity were observed during the afternoon of this phase. In summary, the effe cts of THC on TIDA activity, the sensitivity of the anterior pituitary to DA and PRL release seem to be under gonadal influence. This can be concluded from the observations that THC treatment caused different e ffects when administered to rats at different stages of the ovarian cy cle. The classical inhibitory effect of THC on PRL release via an enha ncement of TIDA activity observed in males was observed in females onl y during the morning of estrus. Different effects were seen during the diestrus and the afternoon of estrus, whereas its administration duri ng proestrus was ineffective.