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

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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‐HT2/5‐HT1c 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‐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.