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Research ArticleNeuropharmacology

Effects of Repeated 3,4-Methylenedioxymethamphetamine Administration on Neurotransmitter Efflux and Sensory-Evoked Discharge in the Ventral Posterior Medial Thalamus

M. A. Starr, M. E. Page and B. D. Waterhouse
Journal of Pharmacology and Experimental Therapeutics January 2012, 340 (1) 73-82; DOI: https://doi.org/10.1124/jpet.111.185728
M. A. Starr
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M. E. Page
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B. D. Waterhouse
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Abstract

3,4-Methylenedioxymethamphetamine (MDMA) is known to enhance tactile sensory perception, an effect that contributes to its popularity as a recreational drug. The neurophysiological basis for the effects of MDMA on somatosensation are unknown. However, MDMA interactions with the serotonin transporter (SERT) and subsequent enhancement of serotonin neurotransmission are well known. The rat trigeminal somatosensory system receives serotonergic afferents from the dorsal raphe nucleus. Because these fibers express SERT, they should be vulnerable to MDMA-induced effects. We found that administration of a challenge injection of MDMA (3 mg/kg i.p.) after repeated MDMA treatment (3 mg/kg per day for 4 days) elicits both serotonin and norepinephrine efflux in the ventral posterior medial (VPM) thalamus of Long-Evans hooded rats, the main relay along the lemniscal portion of the rodent trigeminal somatosensory pathway. We evaluated the potential for repeated MDMA administration to modulate whisker-evoked discharge of individual neurons in this region. After surgically implanting stainless steel eight-wire multichannel electrode bundles, we recorded spike train activity of single cells while activating the whisker pathway using a piezoelectric mechanical stimulator. We found that repeated MDMA administration increased the spontaneous firing rate but reduced both the magnitude and duration of whisker-evoked discharge in individual VPM thalamic neurons. The time course of drug action on neuronal firing patterns was generally consistent with fluctuations in neurotransmitter efflux as shown from our microdialysis studies. On the basis of these results, we propose that single use and repeated administration of MDMA may “distort,” rather than enhance, tactile experiences in humans, in part, by disrupting normal spike firing patterns through somatosensory thalamic relay circuits.

Footnotes

  • This work was supported by the National Institutes of Health National Institute on Drug Abuse [Grants 1-F31-DA018469-01A, R21-DA023711].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    http://dx.doi.org/10.1124/jpet.111.185728.

  • ↵Embedded Image The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    MDMA
    3,4-methylenedioxymethamphetamine
    5-HT
    serotonin
    NE
    norepinephrine
    VPM
    ventral posterior medial
    HPLC
    high-performance liquid chromatography
    PSTH
    poststimulus time histogram
    SFR
    spontaneous firing rate
    ANOVA
    analysis of variance
    PSD
    power spectral density.

  • Received July 1, 2011.
  • Accepted September 29, 2011.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 340 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 340, Issue 1
1 Jan 2012
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Research ArticleNeuropharmacology

Effects of MDMA on Sensory Processing in VPM Thalamus

M. A. Starr, M. E. Page and B. D. Waterhouse
Journal of Pharmacology and Experimental Therapeutics January 1, 2012, 340 (1) 73-82; DOI: https://doi.org/10.1124/jpet.111.185728

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Research ArticleNeuropharmacology

Effects of MDMA on Sensory Processing in VPM Thalamus

M. A. Starr, M. E. Page and B. D. Waterhouse
Journal of Pharmacology and Experimental Therapeutics January 1, 2012, 340 (1) 73-82; DOI: https://doi.org/10.1124/jpet.111.185728
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