Mice lacking the long splice variant of the γ2 subunit of the GABA(A) receptor Are more sensitive to benzodiazepines

Pharmacology Biochemistry and Behavior

Volumn 66, Issue 2, 2000, Pages 371-374

  Quinlan, Joseph J ^a   Firestone, Leonard L ^a   Homanics, Gregg E ^a  

^a UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

CCM; 2 Subunit: 2 splice variant; Benzodiazepines; Diazepam; GABA(A) receptor; Gene deletion; Mice; Midazolam; Ro15 4513; Zolpidem

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; 8 AZIDO 5,6 DIHYDRO 5 METHYL 6 OXO 4H IMIDAZO[1,5 A][1,4]BENZODIAZEPINE 3 CARBOXYLIC ACID ETHYL ESTER; BENZODIAZEPINE DERIVATIVE; BENZODIAZEPINE RECEPTOR STIMULATING AGENT; BETA CARBOLINE 3 CARBOXYLIC ACID METHYL ESTER; DIAZEPAM; ETOMIDATE; FLUMAZENIL; MIDAZOLAM; MUSCIMOL; PENTOBARBITAL; RECEPTOR SUBUNIT; ZOLPIDEM;

ANIMAL TISSUE; ANXIETY; ARTICLE; BRAIN HOMOGENATE; BRAIN MEMBRANE; CONTROLLED STUDY; DRUG RECEPTOR BINDING; FEMALE; GENE DELETION; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RECEPTOR AFFINITY; RNA SPLICING; SLEEP TIME;

ALTERNATIVE SPLICING; ANIMALS; AZIDES; BENZODIAZEPINES; BRAIN; CARBOLINES; DIAZEPAM; DRUG RESISTANCE; FEMALE; FLUMAZENIL; GABA MODULATORS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MIDAZOLAM; PYRIDINES; RECEPTORS, GABA-A; SLEEP; VARIATION (GENETICS);

EID: 0034086103     PISSN: 00913057     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0091-3057(00)00225-2     Document Type: Article

References (19)

1. Alifimoff J.K., Firestone L.L., Miller K.W. Anesthetic potencies of secondary alcohol isomers. Anesthesiology. 66:1987;55-59.
2. Gunther U., Benson J., Benke D., Fritschy J., Reyes G., Knoflach F., Crestani F., Aguzzi A., Argoni M., Lang Y., Bluethmann H., Mohler H., Luscher B. Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors. Proc. Natl. Acad. Sci. USA. 92:1995;7749-7753.
3. A receptor in rat brain. J. Neurosci. 14:1994;7168-7179.
4. Haefely W.E. Benzodiazepines. Int. Anesthesiol. Clin. 26:1988;262-272.
5. A receptors expressed in mannalian cells and Xenopus oocytes. Alcohol. Clin. Exp. Res. 21:1997;444-451.
6. Homanics G.E., Harrison N.L., Quinlan J.J., Krasowski M.D., Rick C.E.M., de Blas A.L., Mehta A.K., Kist F., Mihalek R.M., Aul J.J., Firestone L.L. Normal electrophysiological and behavioral responses to ethanol in mice lacking the long splice variant of the γ2 subunit of the γ-aminobutyrae type A receptor. Neuropharmacology. 38:1999;253-255.
7. Homanics G.E., Ferguson C., Quinlan J.J., Daggett J., Snyder K., Lagenaur C., Mi Z., Wang X., Grayson D.R., Firestone L.L. Gene knockout of the α6 subunit of the γ-aminobutyric acid type A receptor. Lack of effect on responses to ethanol, pentobarbital, and general anesthetics Mol. Pharmacol. 51:1997;588-596.
8. Homanics G.E., Quinlan J.J., Firestone L.L. Pharmacologic and behavioral responses of inbred C57BL/6J and Strain 129/SvJ mouse lines. Pharmacol. Biochem. Behav. 63:1999;21-26.
9. A receptor selective for a behavioural alcohol antagonist. Nature. 346:1990;648-651.
10. Marley R.J., Miner L.L., Wehner J.M., Collins A.C. Differential effects of central nervous system depressants in long-sleep and short-sleep mice. J. Pharmacol. Exp. Ther. 238:1986;1028-1033.
11. A receptor-mediated currents. Lack of subunit specificity Eur. J. Pharmacol. 268:1994;209-214.
12. Quinlan J.J., Firestone L.L. Ligand-dependent effects of ethanol and diethylether at brain benzodiazepine receptors. Pharmacol. Biochem. Behav. 42:1992;787-790.
13. Quinlan J.J., Homanics G.E., Firestone L.L. Anesthesia sensitivity in mice that lack the β3 subunit of the γ-aminobutyric acid type A receptor. Anesthesiology. 88:1998;775-780.
14. A receptor function and ethanol. FEBS Lett. 324:1993;140-142.
15. A/benzodiazepine receptors. Mol. Pharmacol. 44:1993;437-442.
16. A receptors requires phosphorylation of the alternatively spliced variant of the γ2 subunit. FEBS Lett. 313:1992;133-137.
17. Waud D.R. On biological assays involving quantal responses. J. Pharmacol. Exp. Ther. 183:1972;577-597.
18. Whiting P., McKernan R.M., Iversen L.L. Another mechanism for creating diversity in γ-aminobutyrate type A receptors. RNA splicing directs expression of two forms of γ2 subunit, one of which contains a protein kinase C phosphorylation site Proc. Natl. Acad. Sci. USA. 87:1990;9966-9970.
19. A receptor. J. Med. Chem. 37:1994;4576-4580.