PMID- 17350761
OWN - NLM
STAT- MEDLINE
DCOM- 20070706
LR  - 20131121
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 416
IP  - 3
DP  - 2007 Apr 18
TI  - Etomidate and propofol-hyposensitive GABAA receptor beta3(N265M) mice show little 
      changes in acute alcohol sensitivity but enhanced tolerance and withdrawal.
PG  - 275-8
AB  - Gamma-aminobutyric acid-A (GABAA) receptors are ligand-gated ion channels 
      comprised of subunits from several classes (alpha, beta, gamma, delta). Recent 
      studies have clearly demonstrated that the functional properties of GABAA 
      receptors are altered following chronic ethanol administration that could provide 
      the molecular basis for the previously proposed role of these receptors in 
      ethanol tolerance and dependence. Because the subunit composition of GABAA 
      receptors determines receptor pharmacology, the present study was devoted to 
      assess if the behavioral sensitivity after acute and chronic ethanol exposure 
      depends on beta3-containing GABAA receptors. In the present study, we used 
      knock-in mice harboring a point mutation (N265M) in the second transmembrane 
      region of the beta3 subunit of the GABAA receptor in order to study acute and 
      chronic behavioral effects of ethanol. More specifically, we tested tolerance to 
      loss of righting reflex (LORR) and the development of withdrawal signs after 
      chronic ethanol exposure using ethanol vapor chambers. Our results show that the 
      beta3(N265M) mutation does not play a major modulatory role of acute 
      ethanol-induced LORR. However, following repeated LORR testing, enhanced 
      tolerance to the intoxicating effects of ethanol was observed--a finding which 
      was unrelated to the pharmacokinetics of ethanol as both genotypes had the same 
      blood alcohol concentrations following repeated LORR testing. In addition, 
      following chronic alcohol vapor exposure, mouse mutants displayed increased 
      handling-induced convulsions during withdrawal. The results of the present study 
      suggest that the alcohol effects abolished by the beta3(N265M) mutation do not 
      play a dominant role in acute alcohol intoxication but influence ethanol 
      tolerance and withdrawal.
FAU - Sanchis-Segura, Carles
AU  - Sanchis-Segura C
AD  - Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, 
      Germany.
FAU - Cline, Brandon
AU  - Cline B
FAU - Jurd, Rachel
AU  - Jurd R
FAU - Rudolph, Uwe
AU  - Rudolph U
FAU - Spanagel, Rainer
AU  - Spanagel R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070211
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Receptors, GABA-A)
RN  - 3K9958V90M (Ethanol)
RN  - 7006-34-0 (Asparagine)
RN  - AE28F7PNPL (Methionine)
RN  - YI7VU623SF (Propofol)
RN  - Z22628B598 (Etomidate)
SB  - IM
MH  - Alcohol-Induced Disorders/*genetics/physiopathology
MH  - Analysis of Variance
MH  - Animals
MH  - Asparagine/genetics
MH  - Drug Tolerance/*genetics
MH  - Ethanol/administration & dosage/blood
MH  - Etomidate/*administration & dosage
MH  - Hypnotics and Sedatives/*administration & dosage
MH  - Methionine/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Propofol/*administration & dosage
MH  - Receptors, GABA-A/*genetics
MH  - Reflex/drug effects
EDAT- 2007/03/14 09:00
MHDA- 2007/07/07 09:00
CRDT- 2007/03/14 09:00
PHST- 2007/01/05 00:00 [received]
PHST- 2007/02/06 00:00 [revised]
PHST- 2007/02/06 00:00 [accepted]
PHST- 2007/03/14 09:00 [pubmed]
PHST- 2007/07/07 09:00 [medline]
PHST- 2007/03/14 09:00 [entrez]
AID - S0304-3940(07)00177-2 [pii]
AID - 10.1016/j.neulet.2007.02.024 [doi]
PST - ppublish
SO  - Neurosci Lett. 2007 Apr 18;416(3):275-8. doi: 10.1016/j.neulet.2007.02.024. Epub 
      2007 Feb 11.