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A role for the mesolimbic dopamine system in the psychostimulant actions of MDMA
L H Gold1, C B Hubner, G F Koob
1Department of Basic and Clinical Research, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Abstract:
Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with a chemical structure that resembles both the amphetamines and mescaline and has both stimulant and perception altering properties. The stimulant properties of MDMA were assessed in photocell cages designed to measure locomotor activity in rats. MDMA, over a range of doses (2.5-10.0 mg/kg, SC) produced locomotor hyperactivity which lasted up to 4 h. Further studies examined the role of the mesolimbic dopamine system in the hyperactivity induced by MDMA. 6-Hydroxydopamine lesions of the Nucleus accumbens attenuated the locomotor response produced by MDMA. The well characterized attenuation of the locomotor response produced by amphetamine was also demonstrated in the same rats. The present study demonstrates similarities in the stimulant properties of MDMA and amphetamine, and also suggests that as with amphetamine, the locomotor activation associated with MDMA may involve the presynaptic release of dopamine in the region of the Nucleus accumbens. However, MDMA may have a more unusual pharmacological profile because of its longer duration of action, neurotoxic potential, and differences in the qualitative aspects of its psychoactive effects.
Insights
Methylenedioxymethamphetamine (MDMA) causes stimulant-induced hyperactivity in rats, similar to amphetamine. This effect appears to involve dopamine release in the Nucleus accumbens, suggesting shared stimulant mechanisms.
Area of Science:
- Neuroscience
- Pharmacology
- Psychopharmacology
Background:
- Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with stimulant and perceptual altering properties.
- Its stimulant effects share structural similarities with amphetamines and mescaline.
Purpose of the Study:
- To assess the stimulant properties of MDMA in rats.
- To investigate the role of the mesolimbic dopamine system in MDMA-induced hyperactivity.
Main Methods:
- Locomotor activity was measured in photocell cages after administering various doses of MDMA (2.5-10.0 mg/kg, SC).
- 6-Hydroxydopamine lesions of the Nucleus accumbens were used to examine dopamine system involvement.
- Comparisons were made with the effects of amphetamine in the same animal model.
Main Results:
- MDMA produced dose-dependent locomotor hyperactivity lasting up to 4 hours.
- Lesions of the Nucleus accumbens attenuated the locomotor response to MDMA.
- The results showed similarities between MDMA and amphetamine's stimulant effects.
Conclusions:
- MDMA exhibits stimulant properties comparable to amphetamine.
- Locomotor activation by MDMA likely involves presynaptic dopamine release in the Nucleus accumbens.
- MDMA's pharmacological profile may be distinct due to its longer duration, neurotoxicity, and unique psychoactive effects.