PMID- 21996653
OWN - NLM
STAT- MEDLINE
DCOM- 20120709
LR  - 20151119
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 33
IP  - 2
DP  - 2012 Mar
TI  - Methamphetamine, amphetamine, MDMA ('ecstasy'), MDA and mCPP modulate electrical 
      and cholinergic input in PC12 cells.
PG  - 255-60
LID - 10.1016/j.neuro.2011.09.003 [doi]
AB  - Reversal of the dopamine (DA) membrane transporter is the main mechanism through 
      which many drugs of abuse increase DA levels. However, drug-induced modulation of 
      exocytotic DA release by electrical (depolarization) and neurochemical inputs 
      (e.g., acetylcholine (ACh)) may also contribute. We therefore investigated 
      effects of methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine 
      (MDMA), 3,4-methylenedioxyamphetamine (MDA) and meta-chlorophenylpiperazine 
      (mCPP) (1-1000 muM) on these inputs by measuring drug-induced changes in basal, 
      depolarization- and ACh-evoked intracellular calcium concentrations ([Ca(2+)](i)) 
      using a dopaminergic model (PC12 cells) and Fura 2 calcium imaging. The strongest 
      drug-induced effects were observed on cholinergic input. At 0.1mM all drugs 
      inhibited the ACh-evoked [Ca(2+)](i) increases by 40-75%, whereas ACh-evoked 
      [Ca(2+)](i) increases were nearly abolished following higher drug exposure (1mM, 
      80-97% inhibition). Additionally, high MDMA and mCPP concentrations increased 
      basal [Ca(2+)](i), but only following prior stimulation with ACh. Interestingly, 
      low concentrations of methamphetamine or amphetamine (10 muM) potentiated 
      ACh-evoked [Ca(2+)](i) increases. Depolarization-evoked [Ca(2+)](i) increases 
      were also inhibited following exposure to high drug concentrations, although 
      drugs were less potent on this endpoint. Our data demonstrate that at high drug 
      concentrations all tested drugs reduce stimulation-evoked increases in 
      [Ca(2+)](i), thereby probably reducing dopaminergic output through inhibition of 
      electrical and cholinergic input. Furthermore, the increases in basal [Ca(2+)](i) 
      at high concentrations of MDMA and mCPP likely increases dopaminergic output. 
      Similarly, the increases in ACh-evoked [Ca(2+)](i) upon cholinergic stimulation 
      following exposure to low concentrations of amphetamines can contribute to 
      drug-induced increases in DA levels observed in vivo. Finally, this study shows 
      that mCPP, which is regularly found in ecstasy tablets, is the most potent drug 
      regarding the investigated endpoints.
CI  - Copyright A(c) 2011 Elsevier Inc. All rights reserved.
FAU - Hondebrink, Laura
AU  - Hondebrink L
AD  - Neurotoxicology Research Group, Institute for Risk Assessment Sciences (IRAS), 
      Utrecht University, P.O. Box 80.177, NL-3508 TD Utrecht, The Netherlands. 
      L.Hondebrink@umcutrecht.nl
FAU - Meulenbelt, Jan
AU  - Meulenbelt J
FAU - Rietjens, Saskia J
AU  - Rietjens SJ
FAU - Meijer, Marieke
AU  - Meijer M
FAU - Westerink, Remco H S
AU  - Westerink RH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111004
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Adrenergic Agents)
RN  - 0 (Cholinergic Agents)
RN  - 0 (Piperazines)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 44RAL3456C (Methamphetamine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 660YQ98I10 (Potassium Chloride)
RN  - CK833KGX7E (Amphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - REY0CNO998 (1-(3-chlorophenyl)piperazine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine
MH  - Adrenergic Agents/*pharmacology
MH  - Amphetamine
MH  - Animals
MH  - Calcium/metabolism
MH  - Cholinergic Agents/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Membrane Potentials/*drug effects
MH  - Methamphetamine
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - PC12 Cells
MH  - Piperazines
MH  - Potassium Chloride/pharmacology
MH  - Rats
MH  - Serotonin Receptor Agonists/*pharmacology
EDAT- 2011/10/15 06:00
MHDA- 2012/07/10 06:00
CRDT- 2011/10/15 06:00
PHST- 2011/08/14 00:00 [received]
PHST- 2011/09/11 00:00 [accepted]
PHST- 2011/10/15 06:00 [entrez]
PHST- 2011/10/15 06:00 [pubmed]
PHST- 2012/07/10 06:00 [medline]
AID - S0161-813X(11)00169-0 [pii]
AID - 10.1016/j.neuro.2011.09.003 [doi]
PST - ppublish
SO  - Neurotoxicology. 2012 Mar;33(2):255-60. doi: 10.1016/j.neuro.2011.09.003. Epub 
      2011 Oct 4.