PMID- 14559429
OWN - NLM
STAT- MEDLINE
DCOM- 20040608
LR  - 20191108
IS  - 1089-8603 (Print)
IS  - 1089-8603 (Linking)
VI  - 9
IP  - 1
DP  - 2003 Aug
TI  - Inhibition of neuronal nitric oxide synthase suppresses the maintenance but not 
      the induction of psychomotor sensitization to MDMA ('Ecstasy') and 
      p-chloroamphetamine in mice.
PG  - 24-32
AB  - Repeated exposure to psychostimulants such as cocaine and amphetamines results in 
      behavioral sensitization, a paradigm thought to be relevant to drug craving and 
      addiction in humans. We have previously shown that the induction, expression, and 
      maintenance of psychomotor sensitization to cocaine, methamphetamine, and 
      methylphenidate (indirect dopamine agonists) are blocked by co-administration of 
      the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI). In 
      the present study, we investigated the effects of 7-NI on the induction, 
      expression, and maintenance of psychomotor sensitization to 
      3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') and p-chloroamphetamine 
      (PCA). The following observations are reported: (a) Repeated administration of 
      MDMA (10 mg/kg) and PCA (5 mg/kg) to Swiss Webster mice for six consecutive days 
      caused a 3-fold increase in the psychomotor stimulating effect of the drugs on 
      day 6 compared to day 1. (b) Pretreatment with 7-NI (25 mg/kg) did not affect the 
      induction and expression of sensitization to MDMA and PCA. (c) Pretreatment with 
      7-NI did, however, suppress the enduring sensitized response to challenge 
      injections of MDMA and PCA which was observed in mice pretreated with vehicle 
      instead of 7-NI. (d) Unlike other psychostimulants, MDMA and PCA treatment did 
      not produce conditioned (context-dependent) hyperlocomotion. These findings, 
      coupled with our previous studies, suggest the following: (a) The induction and 
      expression of psychomotor sensitization to MDMA and PCA are independent of nNOS 
      activity and involve primarily serotonergic transmission. (b) The maintenance of 
      psychomotor sensitization is dependent on intact nNOS activity and involves 
      primarily dopaminergic transmission.
FAU - Anderson, Karen L
AU  - Anderson KL
AD  - Department of Psychiatry and Behavioral Science, University of Miami School of 
      Medicine, Miami, FL 33136, USA.
FAU - Itzhak, Yossef
AU  - Itzhak Y
LA  - eng
GR  - DA 12867/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  - Nitric Oxide
JT  - Nitric oxide : biology and chemistry
JID - 9709307
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indazoles)
RN  - 0 (Serotonin Agents)
RN  - 64-12-0 (p-Chloroamphetamine)
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)
RN  - UX0N37CMVH (7-nitroindazole)
SB  - IM
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/*pharmacology
MH  - Indazoles/pharmacology
MH  - Locomotion/drug effects
MH  - Male
MH  - Mice
MH  - Motor Activity/*drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neuronal Plasticity/drug effects
MH  - Nitric Oxide Synthase/antagonists & inhibitors/*metabolism
MH  - Nitric Oxide Synthase Type I
MH  - Psychomotor Performance/drug effects
MH  - Serotonin Agents/*pharmacology
MH  - Time Factors
MH  - p-Chloroamphetamine/*pharmacology
EDAT- 2003/10/16 05:00
MHDA- 2004/06/21 10:00
CRDT- 2003/10/16 05:00
PHST- 2003/10/16 05:00 [pubmed]
PHST- 2004/06/21 10:00 [medline]
PHST- 2003/10/16 05:00 [entrez]
AID - S1089860303000466 [pii]
AID - 10.1016/s1089-8603(03)00046-6 [doi]
PST - ppublish
SO  - Nitric Oxide. 2003 Aug;9(1):24-32. doi: 10.1016/s1089-8603(03)00046-6.