Lasting effects of (±)-3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in nonhuman primates: Neurochemical observations

George Ricaurte, A. L. Martello, J. L. Katz, M. B. Martello

Research output: Contribution to journalArticle

Abstract

The purpose of this study was to assess the duration of (±)-3,4- methylenedioxymethamphetamine's (MDMA's) effects on serotonin containing neurons in nonhuman primates. Fifteen squirrel monkeys were used: three served as controls, 12 received MDMA s.c. at a dose of 5 mg/kg twice daily for 4 consecutive days. Two weeks, 10 weeks, 8 months and 18 months after drug treatment, groups (n = 3) of MDMA-treated monkeys, along with controls, were examined for regional brain content of serotonin and 5- hydroxyindoleacetic acid, and for the number of [3H] paroxetine-labeled serotonin uptake sites. Two weeks after MDMA treatment, monkeys showed profound reductions in all three serotonergic presynaptic markers. By 10 weeks, there was evidence of partial recovery in some brain regions (e.g., hippocampus, caudate nucleus, frontal cortex). However, by 18 months, it was evident that recovery did not continue, as serotonergic deficits returned to the level of severity observed 2 weeks after MDMA treatment. This was the case in all brain regions examined except the thalamus and hypothalamus. In the thalamus, the level of serotonin increased to 63% of control, whereas that of 5-hydroxyindoleacetic acid recovered completely. In the hypothalamus, concentrations of serotonin and 5-hydroxyindoleacetic acid were 140 and 187% of control, respectively. These results suggest that MDMA produces lasting effects on serotonergic neurons in nonhuman primates, with most brain regions showing evidence of persistent denervation and some showing signs of reinnervation (thalamus) or possibly even hyperinnervation (hypothalamus). The morphological and functional correlates of these enduring neurochemical changes in the MDMA-treated primate remain to be delineated.

Original languageEnglish (US)
Pages (from-to)616-622
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume261
Issue number2
StatePublished - 1992

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Serotonergic Neurons
N-Methyl-3,4-methylenedioxyamphetamine
Primates
Serotonin
Hydroxyindoleacetic Acid
Thalamus
Hypothalamus
Brain
Haplorhini
Saimiri
Paroxetine
Caudate Nucleus
Frontal Lobe
Denervation
Hippocampus
Neurons
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Lasting effects of (±)-3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in nonhuman primates: Neurochemical observations",
abstract = "The purpose of this study was to assess the duration of (±)-3,4- methylenedioxymethamphetamine's (MDMA's) effects on serotonin containing neurons in nonhuman primates. Fifteen squirrel monkeys were used: three served as controls, 12 received MDMA s.c. at a dose of 5 mg/kg twice daily for 4 consecutive days. Two weeks, 10 weeks, 8 months and 18 months after drug treatment, groups (n = 3) of MDMA-treated monkeys, along with controls, were examined for regional brain content of serotonin and 5- hydroxyindoleacetic acid, and for the number of [3H] paroxetine-labeled serotonin uptake sites. Two weeks after MDMA treatment, monkeys showed profound reductions in all three serotonergic presynaptic markers. By 10 weeks, there was evidence of partial recovery in some brain regions (e.g., hippocampus, caudate nucleus, frontal cortex). However, by 18 months, it was evident that recovery did not continue, as serotonergic deficits returned to the level of severity observed 2 weeks after MDMA treatment. This was the case in all brain regions examined except the thalamus and hypothalamus. In the thalamus, the level of serotonin increased to 63{\%} of control, whereas that of 5-hydroxyindoleacetic acid recovered completely. In the hypothalamus, concentrations of serotonin and 5-hydroxyindoleacetic acid were 140 and 187{\%} of control, respectively. These results suggest that MDMA produces lasting effects on serotonergic neurons in nonhuman primates, with most brain regions showing evidence of persistent denervation and some showing signs of reinnervation (thalamus) or possibly even hyperinnervation (hypothalamus). The morphological and functional correlates of these enduring neurochemical changes in the MDMA-treated primate remain to be delineated.",
author = "George Ricaurte and Martello, {A. L.} and Katz, {J. L.} and Martello, {M. B.}",
year = "1992",
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T1 - Lasting effects of (±)-3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in nonhuman primates

T2 - Neurochemical observations

AU - Ricaurte, George

AU - Martello, A. L.

AU - Katz, J. L.

AU - Martello, M. B.

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N2 - The purpose of this study was to assess the duration of (±)-3,4- methylenedioxymethamphetamine's (MDMA's) effects on serotonin containing neurons in nonhuman primates. Fifteen squirrel monkeys were used: three served as controls, 12 received MDMA s.c. at a dose of 5 mg/kg twice daily for 4 consecutive days. Two weeks, 10 weeks, 8 months and 18 months after drug treatment, groups (n = 3) of MDMA-treated monkeys, along with controls, were examined for regional brain content of serotonin and 5- hydroxyindoleacetic acid, and for the number of [3H] paroxetine-labeled serotonin uptake sites. Two weeks after MDMA treatment, monkeys showed profound reductions in all three serotonergic presynaptic markers. By 10 weeks, there was evidence of partial recovery in some brain regions (e.g., hippocampus, caudate nucleus, frontal cortex). However, by 18 months, it was evident that recovery did not continue, as serotonergic deficits returned to the level of severity observed 2 weeks after MDMA treatment. This was the case in all brain regions examined except the thalamus and hypothalamus. In the thalamus, the level of serotonin increased to 63% of control, whereas that of 5-hydroxyindoleacetic acid recovered completely. In the hypothalamus, concentrations of serotonin and 5-hydroxyindoleacetic acid were 140 and 187% of control, respectively. These results suggest that MDMA produces lasting effects on serotonergic neurons in nonhuman primates, with most brain regions showing evidence of persistent denervation and some showing signs of reinnervation (thalamus) or possibly even hyperinnervation (hypothalamus). The morphological and functional correlates of these enduring neurochemical changes in the MDMA-treated primate remain to be delineated.

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