PMID- 18843265
OWN - NLM
STAT- MEDLINE
DCOM- 20090617
LR  - 20240312
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 34
IP  - 6
DP  - 2009 May
TI  - Effects of topiramate and other anti-glutamatergic drugs on the acute 
      intoxicating actions of ethanol in mice: modulation by genetic strain and stress.
PG  - 1454-66
LID - 10.1038/npp.2008.182 [doi]
AB  - Compounds with anti-glutamatergic properties currently in clinical use for 
      various indications (eg Alzheimer's disease, epilepsy, psychosis, mood disorders) 
      have potential utility as novel treatments for alcoholism. Enhanced sensitivity 
      to certain acute intoxicating effects (ataxia, sedative) of alcohol may be one 
      mechanism by which anti-glutamatergic drugs modulate alcohol use. We examined the 
      effects of six compounds (memantine, dextromethorphan, haloperidol, lamotrigine, 
      oxcarbazepine, and topiramate) on sensitivity to acute intoxicating effects of 
      ethanol (ataxia, hypothermia, sedation/hypnosis) in C57BL/6J mice. Analysis of 
      topiramate was extended to determine the influence of genetic background (by 
      comparison of the 129S1, BALB/cJ, C57BL/6J, DBA/2J inbred strains) and prior 
      stress history (by chronic exposure of C57BL/6J to swim stress) on topiramate's 
      effects on ethanol-induced sedation/hypnosis. Results showed that one 
      N-methyl-D-aspartate receptor (NMDAR) antagonist, memantine, but not another, 
      dextromethorphan, potentiated the ataxic but not hypothermic or sedative/hypnotic 
      effects of ethanol. Haloperidol increased ethanol-induced ataxia and 
      sedation/hypnosis to a similar extent as the prototypical NMDAR antagonist 
      MK-801. Of the anticonvulsants tested, lamotrigine accentuated ethanol-induced 
      sedation/hypnosis, whereas oxcarbazepine was without effect. Topiramate was 
      without effect per se under baseline conditions in C57BL/6J, but had a 
      synergistic effect with MK-801 on ethanol-induced sedation/hypnosis. Comparing 
      inbred strains, topiramate was found to significantly potentiate ethanol's 
      sedative/hypnotic effects in BALB/cJ, but not 129S1, C57BL/6J, or DBA/2J strains. 
      Topiramate also increased ethanol-induced sedation/hypnosis in C57BL/6J after 
      exposure to chronic stress exposure. Current data demonstrate that with the 
      exception of MK-801 and haloperidol, the compounds tested had either no 
      significant or assay-selective effects on sensitivity to acute ethanol under 
      baseline conditions in C57BL/6J. However, significant effects of topiramate were 
      revealed as a function of co-treatment with an NMDAR blocker, genetic background, 
      or prior stress history. These findings raise the possibility that topiramate and 
      possibly other anti-glutamatergic drugs could promote the acute intoxicating 
      effects of ethanol in specific subpopulations defined by genetics or life 
      history.
FAU - Chen, Yi-Chyan
AU  - Chen YC
AD  - Department of Psychiatry, Tri-Service General Hospital, National Defense Medical 
      Center, Taipei, Taiwan.
FAU - Holmes, Andrew
AU  - Holmes A
LA  - eng
GR  - Z01 AA000411/ImNIH/Intramural NIH HHS/United States
GR  - Z01 AA000411-04/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20081008
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Excitatory Amino Acid Agents)
RN  - 0 (Triazines)
RN  - 0H73WJJ391 (Topiramate)
RN  - 30237-26-4 (Fructose)
RN  - 33CM23913M (Carbamazepine)
RN  - 3K9958V90M (Ethanol)
RN  - 7355X3ROTS (Dextromethorphan)
RN  - J6292F8L3D (Haloperidol)
RN  - U3H27498KS (Lamotrigine)
RN  - VZI5B1W380 (Oxcarbazepine)
RN  - W8O17SJF3T (Memantine)
SB  - IM
MH  - Alcoholic Intoxication/*drug therapy/*physiopathology
MH  - Animals
MH  - Ataxia/chemically induced/drug therapy
MH  - Carbamazepine/analogs & derivatives/pharmacology
MH  - Central Nervous System Depressants/*pharmacology
MH  - Conscious Sedation
MH  - Dextromethorphan/pharmacology
MH  - Ethanol/*toxicity
MH  - Excitatory Amino Acid Agents/*pharmacology
MH  - Fructose/*analogs & derivatives/pharmacology
MH  - Haloperidol/pharmacology
MH  - Hypothermia/chemically induced/drug therapy
MH  - Lamotrigine
MH  - Male
MH  - Memantine/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Oxcarbazepine
MH  - Species Specificity
MH  - Stress, Psychological/physiopathology
MH  - Topiramate
MH  - Triazines/pharmacology
PMC - PMC2669690
MID - NIHMS69362
EDAT- 2008/10/10 09:00
MHDA- 2009/06/18 09:00
PMCR- 2009/11/01
CRDT- 2008/10/10 09:00
PHST- 2008/10/10 09:00 [pubmed]
PHST- 2009/06/18 09:00 [medline]
PHST- 2008/10/10 09:00 [entrez]
PHST- 2009/11/01 00:00 [pmc-release]
AID - npp2008182 [pii]
AID - 10.1038/npp.2008.182 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2009 May;34(6):1454-66. doi: 10.1038/npp.2008.182. Epub 
      2008 Oct 8.