Effects of LSD on Ca++ currents in central 5-HT-containing neurons: 5-HT1A receptors may play a role in hallucinogenesis.
Drugs that influence the activity of central serotonergic neurons by activating a 5-hydroxytryptamine subtype of receptor (5-HT1A) alter mood and perception. Previously, we demonstrated with whole-cell recordings from acutely isolated 5-HT-containing dorsal raphe (DR) neurons from the adult rat that 5-HT inhibited Ca++ current and activated K+ current in DR neurons. We now show that D-lysergic acid diethylamide (LSD) mimics the actions of 5-HT; it dramatically suppresses Ca++ current in a dose-dependent manner and activates an inwardly rectifying K+ conductance. Spiperone (0.2 microM), 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 microM has no effect on either Ca++ or K+ current by itself, but it competitively antagonizes both effects of LSD. Inhibition of 5-HT release resulting from 5-HT1A receptor activation may play an integral role in the hallucinogenic actions of LSD by reducing competition between 5-HT and LSD for the postsynaptic 5-HT receptors.
Penington
N J
NJ
Department of Pharmacology, State University of New York, HSC Brooklyn.
Fox
A P
AP
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D006212:Hallucinations / Q000139:chemically induced*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology
D015220:Calcium Channels; D015221:Potassium Channels; D011985:Receptors, Serotonin; D012701:Serotonin; D008238:Lysergic Acid Diethylamide