PMID- 17407499
OWN - NLM
STAT- MEDLINE
DCOM- 20070530
LR  - 20131121
IS  - 1355-6215 (Print)
IS  - 1355-6215 (Linking)
VI  - 12
IP  - 1
DP  - 2007 Mar
TI  - The effects of p-chloroamphetamine, methamphetamine and 
      3,4-methylenedioxymethamphetamine (ecstasy) on the gene expression of 
      cytoskeletal proteins in the rat brain.
PG  - 69-80
AB  - Repeated administration of beta-phenylalkylamines is known to produce neuronal 
      changes in the central and peripheral nervous systems of mammals. It is suggested 
      that various components of the cytoskeleton undergo profound alterations after 
      amphetamine use and misuse, contributing to behavioral changes and neurotoxicity. 
      Here we studied the expression of microtubule-associated protein 2 (MAP2) and 
      beta-actin after repeated intraperitoneal applications with equimolar doses of 
      p-chloroamphetamine (PCA), methamphetamine (METH) and 
      3,4-methylenedioxymethamphetamine (MDMA) in the brain of male Wistar rats. 
      Effective (molecular) pharmacological doses (ED) were derived and used for the 
      calculation of (molecular) pharmacological indices (PI). Besides clear but 
      different dose-response curves on the toxicity of the drugs, in situ 
      hybridization and Western blot analysis revealed that repeated administration of 
      these compounds resulted in different substance- and dose-dependent changes in 
      MAP2 gene expression, e.g. in the frontoparietal somatosensoric cortex. In 
      contrast, the expression of beta-actin was not influenced by any of the compounds 
      at the dose levels tested. Lethal doses were determined with 2.1 (PCA), >5.1 
      (METH) and 8.4 mg/kg/day (MDMA). Linear and non-linear repeat-dose lethality was 
      observed for MDMA and PCA, respectively, whereas METH was non-lethal in the dose 
      range used. Values for ED(MAP2) were 0.3, 0.52 and >16.8 mg/kg/day, and therefore 
      those for PI(MAP2) were 20, 4, and 0.5 for METH, PCA and MDMA, respectively. 
      Although the results on mortality did not reflect changes in MAP2 gene 
      expression, they suggest a remarkable difference for those amphetamines without 
      substituents or with a halogen atom at the paraposition of the benzene ring, such 
      as METH or PCA, when compared with MDMA-like substances.
FAU - Putzke, Jorg
AU  - Putzke J
AD  - Institute of Medical Neurobiology, OvG-University, Germany. 
      joerg.putzke@parexel.com
FAU - Spina, Mariarosa G
AU  - Spina MG
FAU - Buchler, Jochen
AU  - Buchler J
FAU - Kovar, Karl-Artur
AU  - Kovar KA
FAU - Wolf, Gerald
AU  - Wolf G
FAU - Smalla, Karl-Heinz
AU  - Smalla KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Addict Biol
JT  - Addiction biology
JID - 9604935
RN  - 0 (Actins)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 44RAL3456C (Methamphetamine)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Actins/*genetics
MH  - Animals
MH  - Blotting, Western
MH  - Brain Mapping
MH  - Central Nervous System Stimulants/*toxicity
MH  - Cerebral Cortex/*drug effects/metabolism/pathology
MH  - Cytoskeletal Proteins/*genetics
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression/*drug effects
MH  - In Situ Hybridization
MH  - Injections, Intraperitoneal
MH  - Male
MH  - Methamphetamine/*toxicity
MH  - Microtubule-Associated Proteins/*genetics
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Rats
MH  - Rats, Wistar
MH  - Survival Analysis
MH  - p-Chloroamphetamine/*toxicity
EDAT- 2007/04/05 09:00
MHDA- 2007/05/31 09:00
CRDT- 2007/04/05 09:00
PHST- 2007/04/05 09:00 [pubmed]
PHST- 2007/05/31 09:00 [medline]
PHST- 2007/04/05 09:00 [entrez]
AID - ADB047 [pii]
AID - 10.1111/j.1369-1600.2006.00047.x [doi]
PST - ppublish
SO  - Addict Biol. 2007 Mar;12(1):69-80. doi: 10.1111/j.1369-1600.2006.00047.x.