Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists.
C W Callaway, M P Johnson, L H Gold, D E Nichols, Mark A. Geyer
Psychopharmacology 1991 DOI: 10.1007/bf02246026 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MBDB fluoxetine S-(+)MDMA p-chloroamphetamine |
| Dose | 1.25, 2.5, 5.0 or 10.0 mg/kg MBDB; 2.5 or 10 mg/kg fluoxetine; 3.0 mg/kg S-(+)MDA; 2.5 mg/kg p-chloroamphetamine; 3.0 mg/kg S-(+)MDMA |
| Duration | 40 minutes after administration for tissue level measurements; hyperactivity lasted greater than 60 minutes after 5.0 and 10.0 mg/kg doses |
| Topics | Serotonin |
| Citations | 70 |
| Key findings | MBDB induces locomotor hyperactivity through serotonin release, not dopamine release, as shown by blockade with fluoxetine. |
Abstract
Derivatives of amphetamine are potent releasers of both dopamine (DA) and serotonin (5-HT), but the relative contributions of DA and 5-HT release to the behavioral effects of these drugs have not been established. Previously, S-(+)3,4-methylenedioxymethamphetamine (S-(+)MDMA) was found to produce locomotor hyperactivity in rats which was dependent on 5-HT release. The present study found that MBDB (1.25, 2.5, 5.0 or 10.0 mg/kg), the alpha-ethyl derivative of MDMA that produces little or no direct DA release, also induced locomotor hyperactivity that lasted for greater than 60 min after the 5.0 and 10.0 mg/kg doses. MBDB produced spatial patterns of locomotor hyperactivity and suppression of exploratory activity (holepokes and rearings) very similar to the behavioral syndrome produced by MDMA. MBDB-induced hyperactivity was blocked by pretreatment with the selective 5-HT uptake inhibitor fluoxetine (2.5 or 10 mg/kg), suggesting that MBDB produced behavioral effects via uptake-carrier mediated release of 5-HT. Similarly, fluoxetine pretreatment blocked the locomotor hyperactivity produced by S-(+)3,4-methylenedioxyamphetamine (3.0 mg/kg) or p-chloroamphetamine (2.5 mg/kg), supporting a serotonergic basis for the action of these drugs. Tissue levels of 5-HT and its metabolite 5-HIAA were decreased 40 min after administration of S-(+)MDMA (3.0 mg/kg) or MBDB (5.0 mg/kg), and these decreases were prevented by fluoxetine pretreatment. S-(+)MDMA also produced a fluoxetine-sensitive increase of tissue DA levels, suggesting that 5-HT release may indirectly result in increased DA release, although MBDB did not significantly increase DA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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 15
- A study of the mechanism of MDMA (‘Ecstasy’)‐induced neurotoxicity of 5‐HT neurones using chlormethiazole, dizocilpine and other protective compounds British Journal of Pharmacology 1994
- Direct effects of 3,4‐methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars reticulata, and the dorsal raphé nucleus slices Synapse April 27, 2000
- Stimulant effects of 3,4-methylenedioxymethamphetamine in the nucleus accumbens of rat. European Journal of Pharmacology April 7, 1992
- Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies Addiction Research & Theory 2002
- N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB): its properties and possible risks. Addiction Biology July 1, 2000
and 10 more in the library
Cites 13
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class Journal of Medicinal Chemistry October 1, 1986
- Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochemical Pharmacology July 15, 1987
- Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Journal of Medicinal Chemistry May 1, 1982
- Neurotoxic effects of the alpha-ethyl homologue of MDMA following subacute administration. Pharmacology, Biochemistry, and Behavior May 1, 1989
and 8 more in the library