Effects of cortical serotonin depletion induced by 3,4-methylenedioxymethamphetamine (MDMA) on behavior, before and after additional cholinergic blockade.
T E Robinson, E Castañeda, I Q Whishaw
Neuropsychopharmacology 1993 DOI: 10.1038/npp.1993.9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled animal experiment Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | 3 4-methylenedioxymethamphetamine (MDMA) |
| Topics | Serotonin MDMA |
| Keywords | Prosencephalon Animals Rats, sprague-dawley N-methyl-3,4-methylenedioxyamphetamine Atropine Random allocation Behavior, animal Male |
| Key findings | Partial depletion of neocortical serotonin (72.6%) after repeated high-dose MDMA did not produce deficits on place navigation learning-set, skilled forelimb use, or complex foraging judgments, and additional cholinergic blockade also produced no deficits. MDMA-pretreated rats showed only a mild impairment in rapidly developing an efficient search strategy, with normal performance once the goal was located and no spatial memory deficit. The authors conclude that this extent of serotonergic denervation is not sufficient to produce marked and lasting behavioral deficits. |
Abstract
Repeated treatment with high doses of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") produces a long-lasting depletion of brain serotonin, presumably because of the degeneration of serotonin axon terminals. However, very little is known about the long-term behavioral consequences of MDMA neurotoxicity. The experiments reported here were designed to evaluate the effects of MDMA neurotoxicity on a number of behavioral tests known to be sensitive to neocortical and hippocampal damage. Also, the effect of additional cholinergic blockade in MDMA-pretreated rats was evaluated because loss of both the serotonergic and cholinergic inputs to the cortex produces a functional decortication and a behavioral syndrome reminiscent of human global dementia. Partial depletion of neocortical serotonin (72.6%) did not produce deficits on a variety of behavioral tests, including a place navigation learning-set task, skilled forelimb use, or the ability to make complex judgements regarding the stimulus properties of food in a foraging situation, and neither did additional cholinergic blockade. MDMA-pretreated rats had a mild impairment in rapidly developing an efficient search strategy in the place navigation task, but once the goal was located, MDMA pretreated rats performed at control levels and showed no deficits in memory for spatial location. It is concluded that the extent of serotonergic denervation produced by MDMA is not sufficient to produce marked and lasting behavioral deficits, possibly because of neurocompensatory changes in the remaining serotonin terminals.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 17
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Deconstructing Ecstasy: The Politics Of Mdma Research Addiction Research & Theory 2000
- MDMA: Its History and Pharmacology Psychiatric Annals March 1, 1994
- Behavioural and neuroendocrine responses to D-fenfluramine in rats treated with neurotoxic amphetamines Journal of Psychopharmacology May 1, 1995
- "Êxtase": revisão farmacológica Revista de Saúde Pública October 1, 1998
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Cites 6
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- 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
- Lasting Neuropsychiatric Sequelae of (??)Methylenedioxymethamphetamine (???Ecstasy???) in Recreational Users Journal of Clinical Psychopharmacology October 1, 1991
- Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. Journal of Pharmacology and Experimental Therapeutics April 1, 1987
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