Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52-week period. Part I: Synaptosomal uptake and tissue concentrations

KE Sabol, R Lew, JB Richards, GL Vosmer and LS Seiden

University of Chicago, Department of Pharmacological and Physiological Sciences, Illinois, USA.

The effects of a high dose methylenedioxymethamphetamine (MDMA) regimen on the serotonin (5-HT) system were evaluated over a 52-wk period. MDMA was administered to rats (20 mg/kg) 8 times at 12-hr intervals. Tissue concentrations of dopamine (DA) and 5-HT, and synaptosomal uptake of 3H- 5-HT and 3H-DA were measured at 2, 8, 16, 32 or 52 wk posttreatment. Synaptosomal uptake of 3H-5-HT (hippocampus) was decreased at 2 and 8 wk, but not at 16, 32 or 52 wk after drug. 5-HT tissue concentrations were measured in frontal cortex, frontal-parietal cortex, occipital- temporal cortex, nucleus accumbens/olfactory tubercle, striatum, amygdala, hippocampus, septum, hypothalamus, ventral tegmentum/substantia nigra. Two weeks after MDMA treatment, all regions showed decreased 5-HT tissue concentrations except septum. Recovery over the 52-wk interval was noted for all depleted regions, but the rate and degree of recovery was region dependent. Frontal-parietal cortex, occipital-temporal cortex and hippocampus showed the least recovery, with significant depletions at 52 wk posttreatment. Hypothalamus showed an increase in 5-HT tissue concentrations relative to age-matched controls at 52 wk. These results indicate that a high- dose MDMA regimen results in long-lasting depletions of serotonin. The rate and degree of recovery of serotonin tissue concentrations seen over the 52-wk test period is region specific.

Volume 276, Issue 2, pp. 846-854, 02/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				A. Green, C. Marsden, and K. Fone MDMA as a clinical tool: a note of caution. A response to Sessa and Nutt J Psychopharmacol, November 1, 2008; 22(8): 929 - 931. [PDF]

				B Sessa and D Nutt Reply to letter by Green, Marsden and Fone (2007) about Sessa and Nutt's editorial (MDMA: baby with the bath water) in the November 2007 Journal J Psychopharmacol, June 1, 2008; 22(4): 457 - 458. [PDF]

				N. Easton and C. A. Marsden Ecstasy: Are animal data consistent between species and can they translate to humans? J Psychopharmacol, March 1, 2006; 20(2): 194 - 210. [Abstract] [PDF]

				E. J. Bull, V. Porkess, M. Rigby, P. H. Hutson, and K. C. F. Fone Pre-treatment with 3,4-methylenedioxymethamphetamine (MDMA) causes long-lasting changes in 5-HT2A receptor-mediated glucose utilization in the rat brain J Psychopharmacol, March 1, 2006; 20(2): 272 - 280. [Abstract] [PDF]

				A. R. Green, A. O. Mechan, J. M. Elliott, E. O'Shea, and M. I. Colado The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") Pharmacol. Rev., September 1, 2003; 55(3): 463 - 508. [Abstract] [Full Text] [PDF]

				L. Reneman, J. Lavalaye, B. Schmand, F. A. de Wolff, W. van den Brink, G. J. den Heeten, and J. Booij Cortical Serotonin Transporter Density and Verbal Memory in Individuals Who Stopped Using 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy"): Preliminary Findings Arch Gen Psychiatry, October 1, 2001; 58(10): 901 - 906. [Abstract] [Full Text] [PDF]

				L. Reneman, C. B. L. M. Majoie, J. B. A. Habraken, and G. J. den Heeten Effects of Ecstasy (MDMA) on the Brain in Abstinent Users: Initial Observations with Diffusion and Perfusion MR Imaging Radiology, September 1, 2001; 220(3): 611 - 617. [Abstract] [Full Text] [PDF]

				K. E. Sabol, J. B. Richards, and K. Yung The Effects of High-Dose Methamphetamine in the Aging Rat: Differential Reinforcement of Low-Rate 72-s Schedule Behavior and Neurochemistry J. Pharmacol. Exp. Ther., September 1, 2000; 294(3): 850 - 863. [Abstract] [Full Text]

				G. Hatzidimitriou, U. D. McCann, and G. A. Ricaurte Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery J. Neurosci., June 15, 1999; 19(12): 5096 - 5107. [Abstract] [Full Text] [PDF]

				J. E. Malberg and L. S. Seiden Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat J. Neurosci., July 1, 1998; 18(13): 5086 - 5094. [Abstract] [Full Text] [PDF]