PMID- 15542708
OWN - NLM
STAT- MEDLINE
DCOM- 20050218
LR  - 20131121
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1025
DP  - 2004 Oct
TI  - Differential response of nNOS knockout mice to MDMA ("ecstasy")- and 
      methamphetamine-induced psychomotor sensitization and neurotoxicity.
PG  - 119-28
AB  - It has been shown that mice deficient in neuronal nitric oxide synthase (nNOS) 
      gene are resistant to cocaine-induced psychomotor sensitization and 
      methamphetamine (METH)-induced dopaminergic neurotoxicity. The present study was 
      undertaken to investigate the hypothesis that nNOS has a major role in dopamine 
      (DA)- but not serotonin (5-hydroxytryptamine; 5-HT)-mediated effects of 
      psychostimulants. The response of nNOS knockout (KO) and wild-type (WT) mice to 
      the psychomotor-stimulating and neurotoxic effects of 
      3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and METH were investigated. 
      Repeated administration of MDMA for 5 days resulted in psychomotor sensitization 
      in both WT and nNOS KO mice, while repeated administration of METH caused 
      psychomotor sensitization in WT but not in KO mice. Sensitization to both MDMA 
      and METH was persistent for 40 days in WT mice, but not in nNOS KO mice. These 
      findings suggest that the induction of psychomotor sensitization to MDMA and METH 
      is NO independent and NO dependent, respectively, while the persistence of 
      sensitization to both drugs is NO dependent. For the neurochemical studies, a 
      high dose of MDMA caused marked depletion of 5-HT in several brain regions of 
      both WT and KO mice, suggesting that the absence of the nNOS gene did not afford 
      protection against MDMA-induced depletion of 5-HT. Striatal dopaminergic 
      neurotoxicity caused by high doses of MDMA and METH in WT mice was partially 
      prevented in KO mice administered with MDMA, but it was fully precluded in KO 
      mice administered with METH. The differential response of nNOS KO mice to the 
      behavioral and neurotoxic effects of MDMA and METH suggests that the nNOS gene is 
      required for the expression and persistence of DA-mediated effects of METH and 
      MDMA, while 5-HT-mediated effects of MDMA (induction of sensitization and 5-HT 
      depletion) are not dependent on nNOS.
FAU - Itzhak, Yossef
AU  - Itzhak Y
AD  - Department of Psychiatry & Behavioral Sciences, University of Miami School of 
      Medicine, Miami, Florida 33136, USA. yitzhak@med.miami.edu
FAU - Anderson, Karen L
AU  - Anderson KL
FAU - Ali, Syed F
AU  - Ali SF
LA  - eng
GR  - R01 DA12867/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Nerve Tissue Proteins)
RN  - 44RAL3456C (Methamphetamine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nos1 protein, mouse)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/enzymology
MH  - Male
MH  - Methamphetamine/*pharmacology/toxicity
MH  - Mice
MH  - Mice, Knockout
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology/toxicity
MH  - Nerve Tissue Proteins/biosynthesis/*deficiency/genetics
MH  - Nitric Oxide Synthase/biosynthesis/*deficiency/genetics
MH  - Nitric Oxide Synthase Type I
MH  - Psychomotor Performance/*drug effects/physiology
EDAT- 2004/11/16 09:00
MHDA- 2005/02/19 09:00
CRDT- 2004/11/16 09:00
PHST- 2004/11/16 09:00 [pubmed]
PHST- 2005/02/19 09:00 [medline]
PHST- 2004/11/16 09:00 [entrez]
AID - 1025/1/119 [pii]
AID - 10.1196/annals.1316.015 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2004 Oct;1025:119-28. doi: 10.1196/annals.1316.015.