LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: Intracellular studies in rat facial motoneurons
Jennifer C. Garratt, Meenakshi Alreja, George K. Aghajanian
Synapse February 1, 1993 DOI: 10.1002/syn.890130205 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Population | Rat facial motoneurons in brain slices |
| Interventions | LSD DOI spiperone ritanserin |
| Topics | Serotonin LSD |
| Keywords | Ritanserin Spiperone Depolarization Current clamp Afterhyperpolarization Hyperpolarization physics Agonist 5-HT Receptor Endocrinology Biophysics Pharmacology Voltage clamp Membrane potential |
| Citations | 46 |
| Key findings | LSD enhances the hyperpolarization-activated cation current I_h more than serotonin does, while producing only a slight depolarization, and this enhancement is blocked by spiperone and ritanserin. |
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.
Comparable studies
Other experimental studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neural correlates of the LSD experience revealed by multimodal neuroimaging. Human participants | 2016 | Experimental study | |
| Crystal structure of an LSD-bound human serotonin receptor | 2017 | Experimental study with structural biology and molecular dynamics simulations | |
| Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Midbrain neurons containing serotonin | 1968 | Experimental study | |
| Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain | 2017 | Experimental study | |
| LSD-Assisted Psychotherapy in Patients with Terminal Cancer Cancer patients | 1973 | Experimental study | n = 60 |
Citations in the library
Cited by 8
- Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives Brain Sciences March 16, 2018
- Adverse consequences of lysergic acid diethylamide Addiction October 1, 1993
- Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Biological Psychiatry May 1, 1996
- LSD-Like Panic From Risperidone in Post-LSD Visual Disorder Journal of Clinical Psychopharmacology June 1, 1996
- Indoleamine and the phenethylamine hallucinogens: mechanisms of psychotomimetic action Drug and Alcohol Dependence June 1, 1998
and 3 more in the library
Cites 5
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis. Journal of Pharmacology and Experimental Therapeutics September 1, 1988
- (+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist. Journal of Pharmacology and Experimental Therapeutics September 1, 1991
- Choroid plexus epithelial cells in primary culture: a model of 5HT1C receptor activation by hallucinogenic drugs. Psychopharmacology 1991
- Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens. Psychopharmacology 1988