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1.
J Pharmacol Exp Ther ; 340(1): 73-82, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21984836

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.


Subject(s)
N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Neurotransmitter Agents/metabolism , Physical Stimulation , Posterior Thalamic Nuclei/metabolism , Serotonin Agents/pharmacology , Animals , Chromatography, High Pressure Liquid , Electrophysiological Phenomena , Evoked Potentials, Somatosensory/physiology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Extracellular Space/drug effects , Extracellular Space/metabolism , Male , Microdialysis , N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage , N-Methyl-3,4-methylenedioxyamphetamine/pharmacokinetics , Norepinephrine/analysis , Norepinephrine/metabolism , Patch-Clamp Techniques , Posterior Thalamic Nuclei/drug effects , Rats , Rats, Long-Evans , Serotonin/analysis , Serotonin/metabolism , Serotonin Agents/administration & dosage , Serotonin Agents/pharmacokinetics , Vibrissae/physiology
2.
J Pharmacol Exp Ther ; 327(1): 20-31, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18606872

ABSTRACT

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.


Subject(s)
N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Neurotransmitter Agents/metabolism , Signal Transduction/drug effects , Thalamus/drug effects , Animals , Dose-Response Relationship, Drug , Male , Malondialdehyde/blood , Motor Activity/drug effects , N-Methyl-3,4-methylenedioxyamphetamine/blood , Norepinephrine/metabolism , Rats , Rats, Long-Evans , Reaction Time/drug effects , Serotonin/metabolism , Thalamus/physiology
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