Effects of sedatives on GABA-mediated chloride flux into cerebral cortical microsacs prepared from emotional and non-emotional mice.
Some strains of rats and mice express increased momentary fear or emotionality when exposed to a novel environment. Previous studies have found significantly fewer diazepam binding sites in the brains of Balb/cJ mice compared to C57BL and AKR/J mice and this has been suggested to contribute to the increased emotionally of the 'nervous' Balb strain. The influx of 36Cl into cerebral cortical microsacs was used to functionally assess the effects of GABA, diazepam and pentobarbital in the Balb mice compared to nonemotional animals (C57 and ICR mice). Slight differences in the ability of GABA to increase chloride influx were found among the three strains. Pentobarbital potentiation of GABA-mediated chloride flux was slightly higher in the ICR mice compared to Balb and C57. Diazepam potentiation of the effects of GABA, however, was significantly decreased in the Balb mice, strengthening the hypothesis that the benzodiazepine receptor is involved in mediating animal emotionality.
Mihic
S J
SJ
Department of Pharmacology, University of Toronto, Ont., Canada.
Van Berckel
B N
BN
O'Dowd
B F
BF
Nguyen
T
T
Wu
P H
PH
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology*; D004357:Drug Synergism; D004644:Emotions; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010424:Pentobarbital / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011963:Receptors, GABA-A / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D002712:Chlorides; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital; D003975:Diazepam