Role of endogenous dopamine in the central serotonergic deficits induced by 3,4-methylenedioxymethamphetamine.
Donna M. Stone, Michel Johnson, Glen R. Hanson, James W. Gibb
Journal of Pharmacology and Experimental Therapeutics October 1, 1988 DOI: 10.1016/s0022-3565(25)20051-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA alpha-methyl-p-tyrosine reserpine 6-hydroxydopamine GBR 12909 |
| Duration | 3 hours and 3 days after MDMA administration |
| Measures | striatal tryptophan hydroxylase (TPH) activity |
| Topics | MDMA Serotonin |
| Key findings | The authors report that endogenous dopamine released by MDMA partially mediates the initial decrease in striatal tryptophan hydroxylase activity and is an important prerequisite for long-term MDMA-induced serotonergic neurotoxicity in rats. Depleting dopamine or blocking its uptake prevented or attenuated these deficits. |
Abstract
Similar to other amphetamine analogs 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), a currently popular illicit drug, has been characterized recently as a serotonergic neurotoxin due to its ability to cause long-lasting deficits in markers of central serotonergic function in animals. Because the serotonergic toxicity associated with the MDMA analog methamphetamine has been linked previously to endogenous dopamine and because MDMA, like methamphetamine, elicits pronounced dopamine release in vitro, we have examined the role of endogenous dopamine in both the immediate (3 hr) and longer-term (3 days) central serotonergic deficits induced by systemic MDMA administration to rats. Depletion of central dopamine content with alpha-methyl-p-tyrosine or reserpine, or selective destruction of nigrostriatal dopamine projections with bilateral 6-hydroxydopamine-induced substantia nigral lesions, partially blocked the immediate MDMA-induced reduction in rat striatal tryptophan hydroxylase (TPH) activity. In addition, the longer-term TPH deficits caused by a high single dose of MDMA were completely prevented by prior alpha-methyl-p-tyrosine or reserpine, and attenuated significantly by inhibition of dopamine uptake with the selective dopamine-uptake blocker GBR 12909. These results implicate endogenous drug-released dopamine as a partial mediator of the initial decrease in TPH activity caused by MDMA and as an important prerequisite to the development of long-term MDMA-induced neurotoxicity. Potential mechanisms of dopamine-mediated toxicity are discussed.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- Neurotoxicity of MDMA and Related Compounds: Anatomic Studiesa Annals of the New York Academy of Sciences October 1, 1990
- Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine Life Science July 24, 2013
- 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine European Journal of Pharmacology November 1, 1992
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