LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: Intracellular studies in rat facial motoneurons

LSD and serotonin (5-HT) both increase the electrical excitability of rat facial motoneurons, but through different mechanisms. While serotonin produces a reversible depolarization of about 5 mV by decreasing resting potassium conductance, LSD causes only a slight depolarization of 1-2 mV. Despite this, LSD strongly enhances the hyperpolarization-activated cation current I_h, more so than serotonin. LSD also attenuates the depolarizing effect of serotonin. The effects of LSD are blocked by the antagonists spiperone and ritanserin, indicating involvement of 5-HT2/5-HT1c receptors. These findings suggest LSD has high efficacy for enhancing I_h current but low efficacy for decreasing potassium conductance.

Study at a glance

Abstract

Abstract 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 (∼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‐HT 2 /5‐HT 1c agonist 1‐(2,5‐dimethoxy‐4‐io‐dophenyl)‐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‐HT 2 /5‐HT 1A antagonist, and by ritanserin, a 5‐HT 2 /5‐HT 1c 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 I h 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 I h current in rat facial motoneurons; possible mechanisms for this difference are discussed. © 1993 Wiley‐Liss, Inc.