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Methylenedioxyamphetamine: a selective effect on cortical content and turnover of 5-HT
1Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
Abstract:
This study examined the effects of the hallucinogen, MDA, on brain content of monoamines and their metabolites in the rabbit. A single 1.8 mg/kg dose of MDA produced 30 to 64% increases in the 5-HT content of frontal cortex from 30 to 120 min after injection and a decrease in 5-HT turnover from 30 min to 8 h, but had no effect in hippocampus, caudate nucleus, or hypothalamus. A single 3.6 mg/kg dose of MDA also reduced the turnover of 5-HT in frontal cortex, but this was accompanied by a decrease in 5-HIAA with no increase in 5-HT. The 1.8 and 3.6 mg/kg doses of MDA had no significant or consistent effects on the contents of DA, DOPAC, HVA, and NE in any brain area examined. Chronic administration of MDA (3.6 mg/kg/day for 4 days) failed to produce any evidence of a neurotoxic action on 5-HT neurons. Higher doses could not be employed because the LD50 of MDA was approximately 5 mg/kg. This study has demonstrated that behaviorally effective and nonneurotoxic doses of MDA produce increases in the content and decreases in turnover of 5-HT in frontal cortex that resemble those of other hallucinogens such as LSD and DOM.
Insights
The hallucinogen MDA increased serotonin (5-HT) in rabbit frontal cortex, similar to other hallucinogens. Non-toxic doses did not harm serotonin neurons, suggesting a specific neurochemical effect.
Area of Science:
- Neuroscience
- Pharmacology
- Psychopharmacology
Background:
- The precise neurochemical mechanisms underlying the effects of psychoactive substances like MDA (3,4-methylenedioxyamphetamine) are not fully understood.
- Investigating the impact of MDA on monoamine neurotransmitters and their metabolites is crucial for comprehending its behavioral and physiological effects.
Purpose of the Study:
- To investigate the effects of MDA on the brain content of monoamines and their metabolites in rabbits.
- To determine if behaviorally effective doses of MDA induce neurotoxic changes in serotonin (5-HT) neurons.
Main Methods:
- Rabbits were administered single or multiple doses of MDA (1.8 mg/kg or 3.6 mg/kg).
- Brain tissue (frontal cortex, hippocampus, caudate nucleus, hypothalamus) was analyzed for levels of 5-HT, dopamine (DA), norepinephrine (NE), and their metabolites (5-HIAA, DOPAC, HVA).
- Serotonin turnover was assessed by measuring the ratio of 5-HIAA to 5-HT.
Main Results:
- A single 1.8 mg/kg dose of MDA increased 5-HT content in the frontal cortex and decreased 5-HT turnover.
- Higher doses or chronic administration did not show significant effects on dopamine or norepinephrine systems.
- Chronic MDA administration did not result in neurotoxic effects on 5-HT neurons at behaviorally relevant doses.
Conclusions:
- Behaviorally effective and non-neurotoxic doses of MDA increase 5-HT content and decrease 5-HT turnover in the frontal cortex.
- These neurochemical changes in the frontal cortex resemble those observed with other hallucinogens like LSD and DOM.
- MDA's primary neurochemical action at non-toxic doses appears to be modulation of the serotonin system in specific brain regions.
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