LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: intracellular studies in rat facial motoneurons.
The effects of LSD (d-lysergic acid diethylamide) on rat facial motoneurons were compared to those of 5-hydroxytryptamine (5-HT) in brain slices by means of current clamp and single-electrode voltage-clamp recordings. As previously reported, 5-HT, in part by decreasing a resting potassium conductance, produced a reversible depolarization (approximately 5 mV), an increase in input resistance, and an enhancement in electrical excitability. LSD also produced an increase in electrical excitability, although with a much slower onset and longer duration. However, in contrast to 5-HT, LSD produced only a slight depolarization (1-2 mV). Moreover, in the presence of LSD the depolarizing effect of 5-HT was markedly attenuated. The 5-HT2/5-HT1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) produced effects intermediate between LSD and 5-HT. The LSD-induced increase in electrical excitability was completely reversed by spiperone, a 5-HT2/5-HT1A antagonist, and by ritanserin, a 5-HT2/5-HT1C antagonist; the effects of 5-HT were also reduced by these 2 antagonists, but complete blockade did not occur at the concentrations and durations tested. Surprisingly, LSD was found to enhance the hyperpolarization-activated nonspecific cation current Ih to a greater extent than did 5-HT; this enhancement was blocked by both spiperone and ritanserin. These results indicate that, despite having low efficacy relative to 5-HT in decreasing resting potassium conductance, LSD has high efficacy in enhancing the Ih current in rat facial motoneurons; possible mechanisms for this difference are discussed.
Garratt
J C
JC
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Alreja
M
M
Aghajanian
G K
GK
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology / Q000379:methods; D005154:Facial Nerve / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology
D016713:Ritanserin; D012701:Serotonin; D013134:Spiperone; D008238:Lysergic Acid Diethylamide