PMID- 10064870
OWN - NLM
STAT- MEDLINE
DCOM- 19990407
LR  - 20190831
IS  - 0165-3806 (Print)
IS  - 0165-3806 (Linking)
VI  - 113
IP  - 1-2
DP  - 1999 Mar 12
TI  - Neurosteroid modulation of the GABAA receptor in the developing guinea pig 
      cerebral cortex.
PG  - 21-8
AB  - Developmental changes in 5alpha-pregnan-3alpha-ol-20-one (allopregnanolone; 
      5alpha-3alpha-P) potentiation of muscimol and benzodiazepine binding to the GABAA 
      receptor were studied in the guinea pig cerebral cortex at three prenatal ages 
      (gestational day (GD) 40, GD 50, GD 62), and three postnatal ages (postnatal day 
      (PD) 11, PD 21, PD 61) (term, about GD 68). The number and affinity of 
      [3H]flunitrazepam binding sites, and 5alpha-3alpha-P potentiation of [3H]muscimol 
      and [3H]flunitrazepam binding to the GABAA receptor were determined at each age. 
      There was no age effect on the affinity (Kd) for [3H]flunitrazepam. However, the 
      number (Bmax) of [3H]flunitrazepam binding sites doubled between GD 40 and GD 62, 
      and then declined slightly to reach adult levels by PD 11. 5alpha-3alpha-P 
      produced a concentration-dependent potentiation of [3H]muscimol and 
      [3H]flunitrazepam binding at each developmental age examined. The potency 
      (high-affinity) for 5alpha-3alpha-P potentiation of both [3H]muscimol and 
      [3H]flunitrazepam binding was lowest at GD 40, and increased to adult levels by 
      GD 62. In contrast, the efficacy for 5alpha-3alpha-P potentiation of both 
      [3H]muscimol and [3H]flunitrazepam binding was greatest at GD 40, and decreased 
      to adult levels between GD 50 and GD 62. The percentage of high-affinity zolpidem 
      binding sites increased in an age-dependent manner from 34.2+/-2.2% at GD 40, to 
      reach adult levels by GD 62 (59. 4+/-2.5%). These data suggest that 
      5alpha-3alpha-P can modulate GABAA receptors in the immature cerebral cortex, and 
      that changes in 5alpha-3alpha-P action are temporally related to changes in GABAA 
      receptor benzodiazepine pharmacology late in gestation in the guinea pig.
CI  - Copyright 1999 Elsevier Science B.V.
FAU - Bailey, C D
AU  - Bailey CD
AD  - Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, 
      Canada.
FAU - Brien, J F
AU  - Brien JF
FAU - Reynolds, J N
AU  - Reynolds JN
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res Dev Brain Res
JT  - Brain research. Developmental brain research
JID - 8908639
RN  - 0 (GABA Agonists)
RN  - 0 (GABA Modulators)
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, GABA-A)
RN  - 10028-17-8 (Tritium)
RN  - 12794-10-4 (Benzodiazepines)
RN  - 2763-96-4 (Muscimol)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 620X0222FQ (Flunitrazepam)
RN  - 7K383OQI23 (Zolpidem)
RN  - BXO86P3XXW (Pregnanolone)
SB  - IM
MH  - Animals
MH  - Benzodiazepines/pharmacology
MH  - Binding, Competitive/physiology
MH  - Brain Chemistry/*drug effects
MH  - Cerebral Cortex/*chemistry/*growth & development
MH  - Female
MH  - Flunitrazepam/pharmacology
MH  - GABA Agonists/pharmacology
MH  - GABA Modulators/*pharmacology
MH  - Guinea Pigs
MH  - Hypnotics and Sedatives/pharmacology
MH  - Male
MH  - Muscimol/pharmacology
MH  - Organ Size
MH  - Pregnanolone/*pharmacology
MH  - Pyridines/pharmacology
MH  - Radioligand Assay
MH  - Receptors, GABA-A/*metabolism
MH  - Tritium
MH  - Zolpidem
MH  - gamma-Aminobutyric Acid/metabolism
EDAT- 1999/03/05 00:00
MHDA- 1999/03/05 00:01
CRDT- 1999/03/05 00:00
PHST- 1999/03/05 00:00 [pubmed]
PHST- 1999/03/05 00:01 [medline]
PHST- 1999/03/05 00:00 [entrez]
AID - S0165-3806(98)00185-0 [pii]
AID - 10.1016/s0165-3806(98)00185-0 [doi]
PST - ppublish
SO  - Brain Res Dev Brain Res. 1999 Mar 12;113(1-2):21-8. doi: 
      10.1016/s0165-3806(98)00185-0.