MDMA (3,4-methylenedioxymethamphetamine)-mediated distortion of somatosensory signal transmission and neurotransmitter efflux in the ventral posterior medial thalamus.
MDMA (3,4-methylenedioxymethamphetamine, Ecstasy) is reported to enhance tactile sensory perception, an effect that is believed to contribute to its popularity as a recreational drug. To date, no literature exists that addresses the neurophysiological mechanisms underlying the effects of MDMA on somatosensation. However, MDMA interactions with the serotonin transporter protein (SERT) are well known. The rat trigeminal somatosensory system has been studied extensively and receives serotonergic afferents from the dorsal raphe nucleus. Given that these fibers express SERT, they should be vulnerable to MDMA-induced effects. We found that short-term low-dose MDMA administration (3 mg/kg i.p.) led to a significant increase in 5-hydroxytryptamine (5-HT) efflux in the ventral posterior medial (VPM) thalamus, the main relay along the lemniscal portion of the rodent trigeminal somatosensory pathway. We further evaluated the potential for MDMA to modulate whisker-evoked discharge (WED) of individual neurons in this region. After surgically implanting stainless steel 8-wire multichannel electrode bundles, we recorded spike train activity from single cells of halothane-anesthetized rats while mechanically activating the whisker pathway. We found that short-term low-dose MDMA (3 mg/kg i.p.) increased the spontaneous firing rate but reduced the magnitude and duration of WED in individual VPM thalamic neurons. It is noteworthy that the time course of drug action on neuronal firing patterns was generally consistent with increased 5-HT efflux as shown from our microdialysis studies. Based on these results, we propose the working hypothesis that MDMA may "distort" rather than enhance tactile experiences in humans, in part, by disrupting normal spike firing patterns through somatosensory thalamic relay circuits.
Starr
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Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA. mla29@drexel.edu
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D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000097:blood / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013788:Thalamus / Q000187:drug effects* / Q000502:physiology
D018377:Neurotransmitter Agents; D012701:Serotonin; D008315:Malondialdehyde; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine