EFFECTS OF LSD ON CA-HT-CONTAINING NEURONS - 5-HT1A RECEPTORS MAY PLAY A ROLE IN HALLUCINOGENESIS(+ CURRENTS IN CENTRAL 5)

Drugs that influence the activity of central serotonergic neurons by a ctivating a 5-hydroxytryptamine subtype of receptor (5-HT1A) alter moo d and perception. Previously, we demonstrated with whole-cell recordin gs from acutely isolated 5-HT-containing dorsal raphe (DR) neurons fro m the adult rat that 5-HT inhibited Ca++ current and activated K+ curr ent in DR neurons. We now show that D-lysergic acid diethylamide (LSD) mimicks the actions of 5-HT; it dramatically suppresses Ca++ current in a dose-dependent manner and activates an inwardly rectifying K+ con ductance. Spiperone (0.2 mu M), a 5-HT1A/5-HT2 antagonist, blocks the effect of both LSD and 5-HT. The nonhallucinogenic structural analog 2 -bromo-LSD (2-Bol) at 10 mu M has no effect on either Ca++ or K+ curre nt by itself, but it competitively antagonizes both effects of LSD. In hibition of 5-HT release resulting from 5-HT1A receptor activation may play an integral role in the hallucinogenic actions of LSD by reducin g competition between 5-HT and LSD for the postsynaptic 5-HT receptors .