LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: Intracellular studies in rat facial motoneurons
Synapse – February 01, 1993
Source: OpenAlex
Summary
LSD significantly enhances electrical excitability in rat facial motoneurons, although it causes only a slight depolarization of 1-2 mV compared to the more substantial 5 mV shift induced by serotonin (5-HT). In experiments with 16 brain slices, LSD's effects were slower and longer-lasting. Importantly, LSD diminished the depolarizing impact of 5-HT and enhanced hyperpolarization-activated cation current (Ih) more than 5-HT did. This enhancement was blocked by spiperone and ritanserin, highlighting LSD's unique pharmacological profile among serotonergic compounds.
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.