PMID- 21984836
OWN - NLM
STAT- MEDLINE
DCOM- 20120202
LR  - 20211020
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 340
IP  - 1
DP  - 2012 Jan
TI  - Effects of repeated 3,4-methylenedioxymethamphetamine administration on 
      neurotransmitter efflux and sensory-evoked discharge in the ventral posterior 
      medial thalamus.
PG  - 73-82
LID - 10.1124/jpet.111.185728 [doi]
AB  - 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.
FAU - Starr, M A
AU  - Starr MA
AD  - Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
FAU - Page, M E
AU  - Page ME
FAU - Waterhouse, B D
AU  - Waterhouse BD
LA  - eng
GR  - F31 DA018469/DA/NIDA NIH HHS/United States
GR  - R21 DA023711/DA/NIDA NIH HHS/United States
GR  - 1-F31-DA018469-01A/DA/NIDA NIH HHS/United States
GR  - R21-DA023711/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111007
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Serotonin Agents)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Electrophysiological Phenomena
MH  - Evoked Potentials, Somatosensory/physiology
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - Extracellular Space/drug effects/metabolism
MH  - Male
MH  - Microdialysis
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & 
      dosage/pharmacokinetics/*pharmacology
MH  - Neurotransmitter Agents/*metabolism
MH  - Norepinephrine/analysis/metabolism
MH  - Patch-Clamp Techniques
MH  - *Physical Stimulation
MH  - Posterior Thalamic Nuclei/drug effects/*metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Serotonin/analysis/metabolism
MH  - Serotonin Agents/administration & dosage/pharmacokinetics/*pharmacology
MH  - Vibrissae/physiology
PMC - PMC3251029
EDAT- 2011/10/11 06:00
MHDA- 2012/02/03 06:00
PMCR- 2013/01/01
CRDT- 2011/10/11 06:00
PHST- 2011/10/11 06:00 [entrez]
PHST- 2011/10/11 06:00 [pubmed]
PHST- 2012/02/03 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - jpet.111.185728 [pii]
AID - 3737519 [pii]
AID - 10.1124/jpet.111.185728 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2012 Jan;340(1):73-82. doi: 10.1124/jpet.111.185728. Epub 
      2011 Oct 7.