Citalopram antagonizes the stimulation by lysergic acid diethylamide of presynaptic inhibitory serotonin autoreceptors in the rat hypothalamus.
Salomón Z. Langer, Chantal Moret
Journal of Pharmacology and Experimental Therapeutics July 1, 1982 DOI: 10.1016/s0022-3565(25)33177-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat hypothalamic slices |
| Interventions | electrical stimulation fenfluramine methiothepin LSD phentolamine sulpiride citalopram |
| Topics | LSD Serotonin |
| Keywords | Autoreceptor Stimulation Fenfluramine Endocrinology Phentolamine 5-HT Receptor Citalopram Neurotransmitter Pharmacology Inhibitory postsynaptic potential Neurotransmission |
| Citations | 100 |
| Key findings | Presynaptic serotonin autoreceptors modulate electrically stimulated, calcium-dependent serotonin release but not calcium-independent fenfluramine-induced release, and LSD inhibits the former via a mechanism antagonized by methiothepin and citalopram. |
Abstract
Slices of rat hypothalamus prelabeled with [3H]-5-hydroxytryptamine ([3H]-5-HT) were superfused and the release of the labeled transmitter was elicited either by electrical stimulation or by fenfluramine. Whereas the electrically stimulated release of [3H]-5-HT was completely abolished by removing calcium from the superfusion medium, the fenfluramine-induced release of [3H]-5-HT was calcium-independent. Methiothepin increased, in a concentration-dependent manner, the [3H]-5-HT release induced by electrical stimulation but had no effect on that elicited by fenfluramine. The 3H-transmitter release elicited by electrical stimulation was inhibited by lysergic acid diethylamide (LSD) in a concentration-dependent manner, but the release induced by fenfluramine was not modified by LSD. The reduction by LSD of [3H]-5-HT overflow elicited by electrical stimulation was antagonized by methiothepin, but unaffected by phentolamine or by sulpiride. Low concentrations (10-1000 nM) of citalopram, a 5-HT uptake inhibitor, antagonized the inhibition by LSD of electrically evoked release of [3H]-5-HT. These concentrations of citalopram did not modify by themselves the overflow of [3H]-5-HT elicited by electrical stimulation. It is concluded that the modulation of [3H]-5-HT release by presynaptic serotonin autoreceptors is not operational when the neurotransmitter is released through a calcium-independent mechanism. The potent presynaptic inhibition by LSD of serotonergic neurotransmission may contribute to the central actions of this drug. The interaction between citalopram and LSD at the level of [3H]-5-HT release does not seem to involve a competitive interaction at the same receptor site. The possibility that neuronal uptake of 5-HT and the presynaptic 5-HT autoreceptor may be linked in a functional manner cannot be excluded.
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 3
- Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD) Psychopharmacology 1987
- MDMA (ecstasy) effects on cultured serotonergic neurons: evidence for Ca2+-dependent toxicity linked to release Brain Research February 1, 1990
- Complex stimulus properties of LSD: a drug discrimination study with alpha 2-adrenoceptor agonists and antagonists. Psychopharmacology August 1995