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Effects of (+-)3,4-methylenedioxymethamphetamine (MDMA) on brain dopaminergic activity in rats
R T Matthews1, T H Champney, G D Frye
1Department of Medical Anatomy, Texas A & M University, College of Medicine, College Station 77843.
Abstract:
Acute treatment with (+-)3,4-methylenedioxymethamphetamine (MDMA) at high doses (10 and 30 mg/kg, IP), but not lower doses increased locomotor activity in male rats. MDMA did not consistently produce any other stereotyped behaviors at any dose. Dopamine (DA) turnover rate as estimated by the ratio of brain tissue levels of 3,4-dihydroxyphenylacetic acid (DOPAC) over DA was decreased in the striatum for up to two hours after acute treatment with 10 mg/kg of MDMA. DA turnover rate was inconsistently decreased in the olfactory tubercle and medial basal hypothalamus, and was unchanged in the medial prefrontal cortex and the substantia nigra/ventral tegmental area. Two hours after a 30 mg/kg injection of MDMA, DA turnover rate was decreased in all brain areas tested. MDMA and d-amphetamine partially reversed a haloperidol-induced elevation of striatal DOPAC levels. In contrast, the nonamphetamine stimulant, amfonelic acid, enhanced haloperidol's effect. In chloral hydrate-anesthesized rats, MDMA injected IV partially inhibited spontaneous firing rate of DA neurons in the substantia nigra (34% decrease at 4 mg/kg of MDMA). Seventeen days after subchronic MDMA treatment (10 or 20 mg/kg, IP, twice per day for four days), DA and DOPAC levels were unchanged in all brain areas tested as compared to levels in control rats. It is concluded that acute treatment with high but not low doses of MDMA has a weak amphetamine-like effect on nigrostriatal as well as mesolimbic/mesocortical and tuberoinfundibular DA neurons in rats. Repeated treatment with MDMA does not appear to be toxic to mesotelencephalic or tuberoinfundibular DA neurons.
Insights
High doses of 3,4-methylenedioxymethamphetamine (MDMA) increase rat locomotor activity and affect dopamine turnover. Repeated MDMA treatment did not show toxicity to dopamine neurons in rats.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- 3,4-methylenedioxymethamphetamine (MDMA) is a psychoactive drug with known effects on neurotransmitter systems.
- Dopamine (DA) plays a crucial role in regulating motor activity and reward pathways.
Purpose of the Study:
- To investigate the acute and subchronic effects of MDMA on locomotor activity and dopamine turnover in male rats.
- To compare the amphetamine-like properties of MDMA on the dopaminergic system.
Main Methods:
- Acute and subchronic administration of MDMA at various doses to male rats.
- Measurement of locomotor activity and stereotyped behaviors.
- Assay of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in different brain regions.
- Electrophysiological recording of dopamine neuron firing rates.
Main Results:
- Acute high-dose MDMA (10 and 30 mg/kg) increased locomotor activity in rats.
- MDMA decreased dopamine turnover in the striatum and other brain areas at high doses.
- MDMA partially reversed haloperidol-induced increases in striatal DOPAC levels.
- Subchronic MDMA treatment did not alter DA or DOPAC levels and did not appear toxic to dopamine neurons.
Conclusions:
- Acute high-dose MDMA exhibits weak amphetamine-like effects on dopaminergic neurons in rats.
- Repeated MDMA administration does not demonstrate neurotoxicity to mesotelencephalic or tuberoinfundibular dopamine neurons.