LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: Intracellular studies in rat facial motoneurons
✍ Scribed by Jennifer C. Garratt; Meenakshi Alreja; George K. Aghajanian
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 999 KB
- Volume
- 13
- Category
- Article
- ISSN
- 0887-4476
No coin nor oath required. For personal study only.
✦ Synopsis
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,/5-HTIc agonist 1-(2,5-dimethoxy-4-i0dophenyl)-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,/5-HTlA antagonist, and by ritanserin, a 5-HT,/5-HTIc 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 1, 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. o 1993 WiIey-Liss, Inc.