Microdialysis studies on 3,4-methylenedioxymethamphetamine-induced dopamine release: effect of dopamine uptake inhibitors.
J F Nash, J Brodkin
Journal of Pharmacology and Experimental Therapeutics November 1, 1991 DOI: 10.1016/s0022-3565(25)20405-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study using in vivo microdialysis Peer reviewed |
|---|---|
| Population | Rats, striatum (anterolateral) |
| Interventions | MDMA mazindol GBR 12909 fluoxetine ketanserin |
| Dose | MDMA 10 microM; mazindol 5 mg/kg i.p.; GBR 12909 10 mg/kg i.p.; fluoxetine 10 mg/kg i.p.; ketanserin 3 mg/kg i.p. |
| Topics | Serotonin MDMA |
| Keywords | Corpus striatum Extracellular space Animals Rats, inbred strains Dopamine N-methyl-3,4-methylenedioxyamphetamine Fluoxetine Piperazines Ketanserin Mazindol Neurotransmitter uptake inhibitors Dialysis Male |
| Key findings | MDMA infused into the rat striatum increased extracellular dopamine in a dose- and time-dependent manner. Pretreatment with the dopamine uptake blockers mazindol or GBR 12909 significantly attenuated this increase, and fluoxetine produced a slight but significant inhibition, while ketanserin had no significant effect. The authors suggest MDMA raises striatal dopamine partly via a carrier-mediated mechanism largely independent of serotonin release. |
Abstract
The effect of dopamine (DA) and serotonin (5-HT) uptake inhibitors on 3,4-methylenedioxymethamphetamine (MDMA)-induced increase in DA efflux was studied using in vivo microdialysis. MDMA was infused directly into the anterolateral striatum via the dialysis probe. The local administration of MDMA produced a dose- and time-dependent increase in the extracellular concentration of DA in the striatum. Peripheral administration of the DA uptake blockers, mazindol (5 mg/kg, i.p.) or GBR 12909 (10 mg/kg, i.p.), produced a slight but significant increase in the extracellular concentration of DA. Moreover, pretreatment with either mazindol or GBR 12909 30 min before the infusion of MDMA (10 microM) significantly attenuated the MDMA-induced increase in the extracellular concentration of DA. Pretreatment with fluoxetine (10 mg/kg, i.p.), a 5-HT uptake blocker, 30 min before the infusion of MDMA produced a slight but significant inhibition of MDMA-induced increase in DA concentration. In contrast, pretreatment with the 5-HT2/1C antagonist, ketanserin (3 mg/kg, i.p.), had no significant effect on the increase in DA concentration produced by the local administration of MDMA. These data are suggestive that MDMA increases the concentration of DA in the striatum, in part, via a carrier-mediated mechanism which is largely independent of its effects on 5-HT release.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 38
- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
- MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? Progress in Neuro-Psychopharmacology and Biological Psychiatry June 8, 2018
- Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. European Journal of Pharmacology November 3, 1994
- Blockade of Striatal 5‐Hydroxytryptmine2Receptors Reduces the Increase in Extracellullar Concentrations of Dopamine Produced by the Amphhetamine analogue 3,4‐Methylenedioxymethamphetamine Journal of Neurochemistry April 1, 1994
- Distinct neural mechanisms for the prosocial and rewarding properties of MDMA Science Translational Medicine December 11, 2019
and 33 more in the library