Long-term central 5-HT depletions resulting from repeated administration of MDMA enhances the effects of single administration of MDMA on schedule-controlled behavior of rats.
A A Li, Gerard J. Marek, Georgetta Vosmer, Lewis S. Seiden
Pharmacology, Biochemistry, and Behavior July 1989 DOI: 10.1016/0091-3057(89)90402-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study (before-and-after repeated-dose design) Peer reviewed |
|---|---|
| Population | Rats performing on a differential-reinforcement-of-low-rate 72-second schedule |
| Intervention | MDMA |
| Dose | single doses of 0.5, 1, 2, 4, and 6 mg/kg; repeated administration of 6 mg/kg twice daily for 4 days |
| Duration | Repeated administration for 4 days, with testing 4 weeks later |
| Topics | MDMA Serotonin |
| Key findings | Single MDMA decreased reinforcement rate (1, 2, 4, 6 mg/kg) and increased response rate (4, 6 mg/kg) in rats on a DRL 72-sec schedule. Four weeks after repeated MDMA (6 mg/kg twice daily for 4 days), sensitivity increased: response-rate increases at 2, 4, and 6 mg/kg and reinforcement-rate decreases at 0.5, 2, and 6 mg/kg were significantly greater than before. Repeated MDMA depleted serotonin by 30-50% in several brain regions without changing norepinephrine or dopamine. The authors suggest serotonergic neurons normally inhibit MDMA's psychomotor stimulant effects and may oppose dopamine in this behavior. |
Abstract
The behavioral effect of single administration of +/- 3,4-methylene-dioxymethamphetamine (MDMA) on rats performing on the differential-reinforcement-of-low-rate 72-second schedule (DRL 72-sec) was compared before and after a period of repeated administration of MDMA known to deplete 5-hydroxytryptamine (5-HT) levels in the brain. Single administration of MDMA decreased reinforcement rate (1, 2, 4, 6 mg/kg) and increased response rate (4,6 mg/kg) of rats performing on the DRL 72-sec schedule. This effect is typical of amphetamines and other psychomotor stimulants. Four weeks after repeated administration of MDMA (6 mg/kg twice daily for 4 days) there was an increase in sensitivity to the effect of single administration of MDMA. Doses of 2, 4 and 6 mg/kg of MDMA resulted in increases in response rate that were significantly greater after repeated MDMA administration than before. Doses of 0.5, 2, and 6 mg/kg of MDMA resulted in decreases of reinforcement rate that were significantly greater after repeated MDMA administration than before. Repeated administration of MDMA resulted in long-term depletion of serotonin levels by 30-50% in the amygdala, neostriatum, hippocampus and the frontal cortex. Norepinephrine and dopamine (DA) levels were not significantly different from control in any of the brain regions analyzed. The behavioral and neurochemical results suggest that serotonergic neurons normally exert an inhibitory action upon the psychomotor stimulant effects of MDMA. Since the psychomotor stimulant effects of amphetamines appear to be mediated primarily by the dopamine system, these results provide evidence that 5-HT and DA may represent opposing systems in the DRL schedule-controlled behavior.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 9
- Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy Journal of Psychopharmacology 2005
- MDMA and memory: the acute and chronic effects of MDMA in pigeons performing under a delayed-matching-to-sample procedure Psychopharmacology February 1, 1993
- Persistent cerebrovascular effects of MDMA and acute responses to the drug European Journal of Neuroscience July 1, 2006
- The effects of binge MDMA on acquisition and reversal learning in a radial-arm maze task. Neurobiology of Learning and Memory March 1, 2011
- Effects of repeated MDMA administration on the motivation for palatable food and extinction of operant responding in mice. Psychopharmacology March 1, 2010
and 4 more in the library
Cites 4
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Journal of Medicinal Chemistry May 1, 1982
- Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. Journal of Pharmacology and Experimental Therapeutics April 1, 1987