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

• Published in: The Journal of pharmacology and experimental therapeutics 2012-01, Vol.340 (1), p.73-82
• Main Authors: Starr, M.A., Page, M.E., Waterhouse, B.D.
• Format: Article
• Language: English
• Subjects: 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; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Neuropharmacology; Neurotransmitter Agents - metabolism; Norepinephrine - analysis; Norepinephrine - metabolism; Patch-Clamp Techniques; Physical Stimulation; Posterior Thalamic Nuclei - drug effects; Posterior Thalamic Nuclei - metabolism; Rats; Rats, Long-Evans; Serotonin - analysis; Serotonin - metabolism; Serotonin Agents - administration & dosage; Serotonin Agents - pharmacokinetics; Serotonin Agents - pharmacology; Vibrissae - physiology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.111.185728

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.