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 this work, we tested this hypothesis in relation to the effects of THC on tuberoinfundibular dopaminergic (TIDA) activity, the anterior pituitary sensitivity to dopamine (DA) and prolactin (PRL) secretion. To this end, we examined the effects of an acute dose of this cannabinoid administered during different phases of the estrous cycle in the morning or afternoon. The results were as follows. THC, administered during the morning of estrus, stimulated TIDA activity as reflected by increases in DA and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents and tyrosine hydroxylase (TH) activity in the medial basal hypothalamus. This 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 receptors and the corresponding decrease in PRL release. By contrast, plasma 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 activity. A similar decrease in the anterior pituitary density of D-2 receptors, but with no changes in plasma PRL levels, was observed when THC was administered during the morning of diestrus. This effect was not accompanied by changes in TIDA activity either. The administration of THC during the afternoon of diestrus stimulated TIDA activity (increases in DA and DOPAC contents and TH activity in the medial basal hypothalamus), as occurred when the cannabinoid was administered during the 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 levels. These results contrast with the absence of significant changes observed when THC was administered during the morning or the afternoon of proestrus, although the highest plasma PRL levels and TIDA activity were observed during the afternoon of this phase. In summary, the effects 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 effects when administered to rats at different stages of the ovarian cycle. The classical inhibitory effect of THC on PRL release via an enhancement of TIDA activity observed in males was observed in females only during the morning of estrus. Different effects were seen during the diestrus and the afternoon of estrus, whereas its administration during proestrus was ineffective.