Effects of Glutamate Antagonists on Methamphetamine and 3,4‐Methylenedioxymethamphetamine‐Induced Striatal Dopamine Release In Vivo
Kevin T. Finnegan, Terri Taraska
Journal of Neurochemistry May 1, 1996 DOI: 10.1046/j.1471-4159.1996.66051949.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vivo animal study Peer reviewed |
|---|---|
| Population | Rats (striatum) |
| Interventions | Methamphetamine (METH) 3 4-methylenedioxymethamphetamine (MDMA) MK-801 CGS 19755 6-cyano-7-nitro-quinoxaline-2 |
| Duration | Animals killed 1 week later |
| Topics | MDMA |
| Citations | 31 |
| Key points | NMDA receptor antagonists MK-801 and CGS 19755 blocked METH- and MDMA-induced persistent depletions of striatal dopamine and serotonin but did not significantly alter stimulant-induced dopamine efflux. The authors argue that neuroprotection by NMDA antagonists does not involve inhibiting dopamine release, and the data do not support tonic glutamate stimulation of striatal dopamine efflux in vivo. |
Abstract
Several amphetamine analogues are reported to increase striatal glutamate efflux in vivo, whereas other data indicate that glutamate is capable of stimulating the efflux of dopamine (DA) in the striatum via a glutamate receptor-dependent mechanism. Based on these findings, it has been proposed that the ability of glutamate receptor-blocking drugs to antagonize the effects of amphetamine may be explained by their capacity to inhibit DA release induced by glutamate. To examine this possibility further, we investigated in vivo the ability of glutamate antagonists to inhibit DA release induced by either methamphetamine (METH) or 3,4-methylenedioxymethamphetamine (MDMA). Both METH and MDMA increased DA efflux in the rat striatum and, in animals killed 1 week later, induced persistent depletions of DA and serotonin in tissue. Pretreatment with MK-801 or CGS 19755 blocked the neurotoxic effects of METH and MDMA but did not significantly alter striatal DA efflux induced by either stimulant. Infusion of 6-cyano-7-nitro-quinoxaline-2,3-dione into the striatum likewise did not alter METH-induced DA overflow, and none of the glutamatergic antagonists affected the basal release of DA when given alone. The findings suggest that the neuroprotective effects of NMDA antagonists do not involve an inhibition of DA release, nor do the data support the proposal that glutamate tonically stimulates striatal DA efflux in vivo. Whether phasic increases in glutamate content might stimulate DA release, however, remains to be determined.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 7
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- MDMA (‘ecstasy’) enhances basal acetylcholine release in brain slices of the rat striatum European Journal of Neuroscience April 1, 2000
- Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA Behavioural Pharmacology May 14, 2015
- Protective Effects of Atorvastatin and Rosuvastatin on 3,4-methylenedioxymethamphetamine (MDMA)-Induced Spatial Learning and Memory Impairment Research Square
- Chronic 3,4-Methylenedioxymethamphetamine (MDMA) Use Is Related to Glutamate and GABA Concentrations in the Striatum But Not the Anterior Cingulate Cortex. The International Journal of Neuropsychopharmacology June 1, 2023
and 2 more in the library