LYSERGIC-ACID DIETHYLAMIDE (LSD) IS A PARTIAL AGONIST OF D-2 DOPAMINERGIC RECEPTORS AND IT POTENTIATES DOPAMINE-MEDIATED PROLACTIN SECRETION IN LACTOTROPHS IN-VITRO

The hallucinogenic effects of lysergic acid diethylamide (LSD) have ma inly been attributed to the interaction of this drug with the serotoni nergic system, but it seems more likely that they are the result of th e complex interactions of the drug with both the serotoninergic and do paminergic systems. The aim of the present study was to investigate th e functional actions of LSD at dopaminergic receptors using prolactin secretion by primary cultures of rat pituitary cells as a model. LSD p roduced a dose-dependent inhibition of prolactin secretion in vitro wi th an IC50 at 1.7x10(-9) M. This action was antagonized by spiperone b ut not by SKF83566 or cyproheptadine, which indicates that LSD has a s pecific effect on D-2 dopaminergic receptors. The maximum inhibition o f prolactin secretion achieved by LSD was lower than that by dopamine (60% versus 80%). Moreover, the fact that LSD at 10(-8) -10(-6) M anta gonized the inhibitory effect of dopamine (10(-7) M) and bromocriptine (10(-11) M) suggests that LSD acts as a partial agonist at D-2 recept ors on lactotrophs in vitro. Interestingly, LSD at 10(-13)-10(-10) M, the concentrations which are 10-1000-fold lower than those required to induce direct inhibition on pituitary prolactin secretion, potentiate d the dopamine (10(-10)-2.5x10(-9) M)-mediated prolactin secretion by pituitary cells in vitro. These results suggest that LSD not only inte racts with dopaminergic receptors but also has a unique capacity for m odulating dopaminergic transmission. These findings may offer new insi ghts into the hallucinogenic effect of LSD.