PMID- 17511969
OWN - NLM
STAT- MEDLINE
DCOM- 20080102
LR  - 20131121
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 62
IP  - 6
DP  - 2007 Sep 15
TI  - Electrophysiologic changes in ventral midbrain dopaminergic neurons resulting 
      from (+/-) -3,4-methylenedioxymethamphetamine (MDMA-"Ecstasy").
PG  - 680-6
AB  - BACKGROUND: Although dopamine (DA) has been implicated in the psychostimulant 
      properties of 3,4-methylenedioxymethamphetamine (MDMA), there is no detailed 
      information on its modalities of action on single ventral midbrain dopaminergic 
      neurons. METHODS: We examined the actions of MDMA on intracellularly recorded 
      dopaminergic neurons maintained in slices. RESULTS: At 1 micromol/L, MDMA 
      depolarized and excited the cells; at 3 micromol/L, either excited or inhibited 
      the neurons. Interestingly, higher concentrations (10-30 micromol/L) inhibited 
      firing through membrane hyperpolarization or caused an outward current. Whereas 
      MDMA's excitatory effects were antagonized by pindolol, indicating involvement of 
      5-HT 1B receptors, the inhibitory effects were counteracted by sulpiride 
      indicating involvement D2 receptors. Treatment of the cells with carbidopa 
      eliminated MDMA-induced firing inhibition and membrane hyperpolarization. MDMA 
      enhanced DA-induced cellular responses but reduced those of amphetamine. 
      Cocaine-induced outward currents were not affected by MDMA. These actions are 
      consistent with inhibition of the DA transporter. Moreover, MDMA depressed the 
      GABA(B) IPSP by activating 5-HT 1B receptors. CONCLUSIONS: Our data demonstrate 
      that 3-30 micromol/L MDMA preferentially inhibits the dopaminergic cells via 
      indirect activation of D2 autoreceptors due to increased extracellular 
      concentration of DA. In contrast, reduction of the GABA(B) IPSP could partially 
      account for excitation caused by 1-3 micromol/L drug.
FAU - Federici, Mauro
AU  - Federici M
AD  - Laboratory of Experimental Neurology, Fondazione Santa Lucia-IRCCS and 
      Neurological Clinic, University of Rome Tor Vergata, Rome, Italy.
FAU - Sebastianelli, Luca
AU  - Sebastianelli L
FAU - Natoli, Silvia
AU  - Natoli S
FAU - Bernardi, Giorgio
AU  - Bernardi G
FAU - Mercuri, Nicola B
AU  - Mercuri NB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070523
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Autoreceptors)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Hallucinogens)
RN  - 0 (Receptors, Dopamine D2)
RN  - BJ4HF6IU1D (Pindolol)
RN  - CK833KGX7E (Amphetamine)
RN  - I5Y540LHVR (Cocaine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - MNX7R8C5VO (Carbidopa)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Action Potentials/drug effects
MH  - Amphetamine/pharmacology
MH  - Animals
MH  - Autoreceptors/drug effects
MH  - Carbidopa/pharmacology
MH  - Cocaine/pharmacology
MH  - Dopamine/physiology
MH  - Dopamine Plasma Membrane Transport Proteins/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Hallucinogens/antagonists & inhibitors/*pharmacology
MH  - Membrane Potentials/drug effects
MH  - Mesencephalon/*drug effects/physiology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/antagonists & inhibitors/*pharmacology
MH  - Neural Inhibition/drug effects
MH  - Neurons/drug effects/physiology
MH  - Pindolol/pharmacology
MH  - Receptors, Dopamine D2/drug effects
MH  - Ventral Tegmental Area/drug effects/physiology
EDAT- 2007/05/22 09:00
MHDA- 2008/01/03 09:00
CRDT- 2007/05/22 09:00
PHST- 2006/10/04 00:00 [received]
PHST- 2006/11/16 00:00 [revised]
PHST- 2006/11/28 00:00 [accepted]
PHST- 2007/05/22 09:00 [pubmed]
PHST- 2008/01/03 09:00 [medline]
PHST- 2007/05/22 09:00 [entrez]
AID - S0006-3223(06)01507-1 [pii]
AID - 10.1016/j.biopsych.2006.11.019 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2007 Sep 15;62(6):680-6. doi: 10.1016/j.biopsych.2006.11.019. 
      Epub 2007 May 23.