Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release.
N L Rempel, C W Callaway, Mark A. Geyer
Neuropsychopharmacology May 1, 1993 DOI: 10.1038/npp.1993.22 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Qualitative Peer reviewed |
|---|---|
| Population | Naive male rats |
| Interventions | RU 24969 Propranolol (+)Propranolol Fluoxetine |
| Dose | RU 24969 1.25 to 5 mg/kg |
| Measures | Behavioral Pattern Monitor (BPM) |
| Topics | Serotonin |
| Keywords | Synapses Animals Rats, sprague-dawley Propranolol N-methyl-3,4-methylenedioxyamphetamine Fluoxetine Scopolamine Nicotine Indoles Caffeine Receptors, serotonin Dopamine agents Designer drugs Behavior, animal Motor activity Dose-response relationship, drug Male Serotonin receptor agonists |
| Key findings | RU 24969 increased locomotor activity with dose and reduced investigatory rearings and holepokes, with repetitive spatial patterns similar to MDMA and unlike amphetamine. Racemic propranolol, but not (+)propranolol, antagonized the hyperactivity, and fluoxetine did not block it. The authors suggest that the locomotor hyperactivity produced by both RU 24969 and MDMA is mediated by activation of 5-HT1B receptors. |
Abstract
The locomotor hyperactivity induced by 3,4-methylene-dioxymethamphetamine (MDMA) and related drugs in rats appears to be due to the drug-induced release of presynaptic serotonin (5-HT). Thus, these drugs increase locomotor activity by acting as indirect 5-HT agonists. The subtype of 5-HT receptor upon which this released 5-HT acts postsynaptically to produce the activating effect of MDMA-like drugs is not known. When tested under conditions in which MDMA increases locomotion, direct agonists at both 5-HT1A and 5-HT1C/2 receptors consistently decrease locomotion. Hence, the present experiments tested the hypothesis that the hyperactivity produced by the release of endogenous 5-HT is due to the activation of 5-HT1B receptors. Using the Behavioral Pattern Monitor (BPM), the profile of behavioral effects of a 5-HT1B agonist, 5-methoxy-3(1,2,3,6)tetrahydropyridin-4yl)-1H-indole (RU 24969), was compared to that previously described for MDMA and related indirect 5-HT agonists. The BPM provided detailed information regarding the amount and qualitative patterning of locomotor activity and investigatory responses in rats. Various doses of RU 24969 (1.25 to 5 mg/kg) were administered to naive male rats 10 minutes prior to placement in the test chambers. As previously reported for MDMA, locomotor activity increased with dose, and investigatory rearings and holepokes decreased. The hyperactivity was characterized by repetitive spatial patterns of locomotion that were qualitatively similar to those produced by indirect 5-HT agonists such as MDMA and dissimilar to those produced by indirect dopamine (DA) agonists such as amphetamine. Pretreatment with racemic propranolol but not (+)propranolol antagonized the hyperactivity induced by RU 24959. Fluoxetine, a 5-HT reuptake inhibitor, failed to block the locomotor activating effects of RU 24969. These findings confirm the similarity between the behavioral effects of RU 24969 and indirect 5-HT agonists and suggest that the locomotor hyperactivity produced by both RU 24969 and MDMA is mediated by the activation of 5-HT1B receptors. Although the effects of MDMA on 5-HT1B receptors are secondary to its ability to release presynaptic 5-HT, the activation produced by RU 24969 appears to be a consequence of its direct agonist effects.
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 19
- Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies Human Psychopharmacology: Clinical and Experimental December 1, 2001
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- 3,4-Methylenedioxymethamphetamine (Ecstasy) Inhibits Dyskinesia Expression and Normalizes Motor Activity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Primates Journal of Neuroscience October 8, 2003
- Effect of Hallucinogens on Unconditioned Behavior Current Topics in Behavioral Neurosciences 2016
- Acute Psychological and Neurophysiological Effects of MDMA in Humans Journal of Psychoactive Drugs June 1, 2002
and 14 more in the library
Cites 4
- 5HT-2 mediation of acute behavioral effects of hallucinogens in rats Psychopharmacology March 1, 1990
- Effects of 5HT-1A agonists on locomotor and investigatory behaviors in rats differ from those of hallucinogens. Psychopharmacology 1989
- Stimulant and hallucinogenic behavioral profiles of 3,4-methylenedioxymethamphetamine and N-ethyl-3,4-methylenedioxyamphetamine in rats. Journal of Pharmacology and Experimental Therapeutics November 1, 1988
- Effects of DOM and DMT in a proposed animal model of hallucinogenic activity. Progress in Neuro-Psychopharmacology and Biological Psychiatry 1985