Effects of chlorimipramine and lysergic acid diethylamide on efflux of precursor-formed 3-H-serotonin: correlations with serotonergic impulse flow.
D. Gallager, George K. Aghajanian
Journal of Pharmacology and Experimental Therapeutics June 1, 1975 DOI: 10.1016/s0022-3565(25)30200-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat brain serotonergic neurons |
| Interventions | d-lysergic acid diethylamide (LSD) chlorimipramine (CIMI) |
| Dose | 75 and 150 mug/kg for LSD; 5 mg/kg and 20 mg/kg for CIMI |
| Topics | LSD Serotonin |
| Citations | 83 |
| Key findings | LSD reduces serotonin efflux by inhibiting impulse flow in serotonergic neurons, while chlorimipramine's effect on serotonin efflux depends on dose, with low doses producing no net change due to compensation by reuptake blockade. |
Abstract
The effects of d-lysergic acid diethylamide (LSD) and chlorimipramine (CIMI) on the firing rate of serotonergic (5-HT) neurons and on the in vivo efflux of 5-HT were investigated in parallel. A cerebroventricular perfusing technique was used to measure the efflux of 3-H-5-HT formed in vivo from 3-H-tryptophan. Impulse flow in serotonergic neurons was monitored by single unit recording from raphe (5-HT) neurons. Doses of LSD and CIMI, which caused a similar degree of inhibition of raphe cell firing, were found to affect 5-HT efflux differently. LSD, at both the 75, and 150 mug/kg doses, produced a similar decrease in 3-H-5-HT efflux. In contrast, CIMI at a low dose (5 mg/kg) did not reduce 5-HT efflux, despite an inhibition in impulse flow. At a high dose (20 mg/kg), CIMI produced an increase in 3-H-5-HT efflux. We conclude that 1) LSD decreased 3-H-5-HT efflux by directly inhibiting impulse flow in 5-HT neurons and/or by a local effect on 5-HT terminals and 2) a low dose of CIMI produces no net change in 3-H-5-HT efflux because a reduction in impulse flow-dependent 5-HT release compensates for blockade by CIMI of 5-HT reuptake.
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 11
- Lysergic Acid Diethylamide- and Mescaline-Induced Attenuation of the Effect of Punishment in the Rat Science May 21, 1976
- Dissociations Between the Effects of LSD on Behavior and Raphe Unit Activity in Freely Moving Cats Science August 3, 1979
- Psilocybin: Biphasic dose-response effects on the acoustic startle reflex in the rat Pharmacology, Biochemistry, and Behavior April 1, 1977
- Interaction between LSD and dopamine D2/3 binding sites in pig brain Synapse 2005
- Mescaline: excitatory effects on acoustic startle are blocked by serotonin2 antagonists Psychopharmacology November 1, 1987
and 6 more in the library