The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens.
Aino Kankaanpää, E Meririnne, P Lillsunde, Timo Seppälä
Pharmacology, Biochemistry, and Behavior April 1998 DOI: 10.1016/s0091-3057(97)00527-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vivo microdialysis study in rats Peer reviewed |
|---|---|
| Population | Conscious, freely moving rats |
| Interventions | Amphetamine 3 2 |
| Dose | Amphetamine 1.0-9.0 mg/kg; MDA 1.0-9.0 mg/kg; MDMA 1.0-9.0 mg/kg; DOM 0.5-1.0 mg/kg |
| Measures | HPLC with electrochemical detection |
| Topics | Serotonin |
| Key points | Amphetamine (1.0-9.0 mg/kg) markedly elevated nucleus accumbens dopamine but did not affect serotonin except at the highest dose, whereas MDA and MDMA (1.0-9.0 mg/kg each) dose-dependently elevated both serotonin and dopamine. DOM (0.5-1.0 mg/kg) did not alter serotonin, which the authors argue suggests extracellular serotonin plays a minor role in hallucinogenic activity and that MDA and MDMA act on serotonergic mechanisms differently from hallucinogens. |
Abstract
The acute effects of amphetamine derivatives on extracellular concentration of serotonin (5-HT) and dopamine in the nucleus accumbens were studied with in vivo microdialysis using conscious, freely moving rats. 5-HT, dopamine, and their major metabolites were measured by HPLC with electrochemical detection. Amphetamine (1.0-9.0 mg/kg) elevated dopamine levels considerably, but failed to affect the levels of 5-HT, except at the highest dose administered. 3,4-Methylenedioxyamphetamine (MDA, 1.0-9.0 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA, 1.0-9.0 mg/kg) elevated both 5-HT and dopamine levels dose dependently. The failure of 2,5-dimethoxy-4-methylamphetamine (DOM, 0.5-1.0 mg/kg) to affect the 5-HT levels suggests that extracellular levels of 5-HT play a minor role in hallucinogenic activity. The strong effects of MDA and MDMA on levels of 5-HT indicate that their actions on serotonergic mechanisms are different from those of the hallucinogens. In addition, methylenedioxyamphetamines may act via dopaminergic mechanisms similar to those of amphetamine.
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 46
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Serotonin 5-HT2BReceptors Are Required for 3,4-Methylenedioxymethamphetamine-Induced Hyperlocomotion and 5-HT ReleaseIn VivoandIn Vitro Journal of Neuroscience March 12, 2008
- Importance of ERK activation in behavioral and biochemical effects induced by MDMA in mice British Journal of Pharmacology October 29, 2003
- Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user Neurology July 25, 2000
and 41 more in the library
Cites 11
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens Journal of Psychoactive Drugs October 1, 1986
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- 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
and 6 more in the library