PMID- 10536021
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 22
DP  - 1999 Oct 26
TI  - Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A
      receptor delta subunit knockout mice.
PG  - 12905-10
AB  - gamma-Aminobutyric acid (GABA) type A receptors mediate fast inhibitory synaptic 
      transmission and have been implicated in responses to sedative/hypnotic agents
      (including neuroactive steroids), anxiety, and learning and memory. Using gene
      targeting technology, we generated a strain of mice deficient in the delta
      subunit of the GABA type A receptors. In vivo testing of various behavioral
      responses revealed a strikingly selective attenuation of responses to neuroactive
      steroids, but not to other modulatory drugs. Electrophysiological recordings from
      hippocampal slices revealed a significantly faster miniature inhibitory
      postsynaptic current decay time in null mice, with no change in miniature
      inhibitory postsynaptic current amplitude or frequency. Learning and memory
      assessed with fear conditioning were normal. These results begin to illuminate
      the novel contributions of the delta subunit to GABA pharmacology and
      sedative/hypnotic responses and behavior and provide insights into the physiology
      of neurosteroids.
FAU - Mihalek, R M
AU  - Mihalek RM
AD  - Department of Anesthesiology, University of Pittsburgh School of Medicine,
      Pittsburgh, PA 15261, USA.
FAU - Banerjee, P K
AU  - Banerjee PK
FAU - Korpi, E R
AU  - Korpi ER
FAU - Quinlan, J J
AU  - Quinlan JJ
FAU - Firestone, L L
AU  - Firestone LL
FAU - Mi, Z P
AU  - Mi ZP
FAU - Lagenaur, C
AU  - Lagenaur C
FAU - Tretter, V
AU  - Tretter V
FAU - Sieghart, W
AU  - Sieghart W
FAU - Anagnostaras, S G
AU  - Anagnostaras SG
FAU - Sage, J R
AU  - Sage JR
FAU - Fanselow, M S
AU  - Fanselow MS
FAU - Guidotti, A
AU  - Guidotti A
FAU - Spigelman, I
AU  - Spigelman I
FAU - Li, Z
AU  - Li Z
FAU - DeLorey, T M
AU  - DeLorey TM
FAU - Olsen, R W
AU  - Olsen RW
FAU - Homanics, G E
AU  - Homanics GE
LA  - eng
GR  - R37 AA010422/AA/NIAAA NIH HHS/United States
GR  - R01 NS028772/NS/NINDS NIH HHS/United States
GR  - AA10422/AA/NIAAA NIH HHS/United States
GR  - GM52035/GM/NIGMS NIH HHS/United States
GR  - NS28772/NS/NINDS NIH HHS/United States
GR  - R01 AA010422/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Azides)
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Receptors, GABA-A)
RN  - 0 (Steroids)
RN  - 12794-10-4 (Benzodiazepines)
RN  - 2763-96-4 (Muscimol)
RN  - 91917-65-6 (Ro 15-4513)
SB  - IM
MH  - Animals
MH  - Azides/metabolism/pharmacology
MH  - Behavior, Animal/*drug effects
MH  - Benzodiazepines/metabolism/pharmacology
MH  - Brain/drug effects/metabolism
MH  - Female
MH  - Hypnotics and Sedatives/metabolism/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Muscimol/metabolism/pharmacology
MH  - Receptors, GABA-A/*genetics/metabolism/physiology
MH  - Sleep Wake Disorders/genetics
MH  - Steroids/metabolism/*pharmacology
PMC - PMC23157
EDAT- 1999/10/27 00:00
MHDA- 1999/10/27 00:01
CRDT- 1999/10/27 00:00
PHST- 1999/10/27 00:00 [pubmed]
PHST- 1999/10/27 00:01 [medline]
PHST- 1999/10/27 00:00 [entrez]
AID - 10.1073/pnas.96.22.12905 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12905-10. doi:
      10.1073/pnas.96.22.12905.