Actions of methoxylated amphetamine hallucinogens on serotonergic neurons of the brain.
N J Penington
Progress in Neuro-Psychopharmacology and Biological Psychiatry August 1996 DOI: 10.1016/0278-5846(96)00076-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Electrophysiological study (in vitro, acutely isolated neurons) Peer reviewed |
|---|---|
| Population | Acutely isolated serotonergic dorsal raphe neurons of the rat |
| Intervention | DOI |
| Dose | 10 microM |
| Topics | Serotonin |
| Key points | DOI at 10 microM had no direct effect on isolated dorsal raphe neurons, failing to activate the inwardly rectifying potassium current, modulate the inward calcium current, or alter glutamate-evoked currents. The authors conclude that DOI does not directly influence dorsal raphe cell bodies and propose that its inhibitory effects after intravenous administration are mediated indirectly. |
Abstract
1. Previous studies of phenethylamine hallucinogenic drugs have reported that intravenous injection of DOI or similar compounds produce an inhibition of the firing rate of serotonergic dorsal raphe neurons of the rat; potentially lowering levels of 5-HT throughout the brain. 2. Direct application by iontophoresis demonstrated only weak non-specific effects, but injection into the nucleus produced slowing of cell firing possibly due to the reduction of on-going synaptic excitation. 3. The literature concerning phenethylamine hallucinogens is discussed in the context of new results obtained from acutely isolated raphe neurons. The effect of DOI (10 microM) was tested on isolated DR neurons that responded to 5-HT with the activation of an inwardly rectifying K+ current but it was without effect. Under conditions that isolated inward Ca2+ current in raphe neurons that was inhibited by 5-HT, DOI was similarly without effect, neither blocking nor mimicking the action of 5-HT. Brief applications of glutamate produced an inward current similar to those produced by synaptic excitation in a slice preparation, but DOI failed to influence the size or duration of these responses. 4. These results suggest that DOI does not directly influence the cell bodies of DR neurons. 5. Further studies using raphe slices subject to synaptic influences will be required to reveal any indirectly mediated mechanism that may underlie the effects of DOI on DR neurons. Alternative indirect mechanisms of DR neuronal inhibition by i.v. DOI and DOM are suggested.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 3
- Learned Helplessness As a Potential Transdiagnostic Therapeutic Mechanism of Classic Psychedelics Psychedelic Medicine June 1, 2023
- Classical psychedelics' action on brain monoaminergic systems. The international journal of biochemistry & cell biology November 1, 2024
- Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology January 20, 2011
Cites 8
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- LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: Intracellular studies in rat facial motoneurons Synapse February 1, 1993
- Dissociations Between the Effects of LSD on Behavior and Raphe Unit Activity in Freely Moving Cats Science August 3, 1979
- (+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist. Journal of Pharmacology and Experimental Therapeutics September 1, 1991
and 3 more in the library