A cholecystokinin-B receptor antagonist potentiates GABAergic and glycinergic inhibition in the nucleus of the solitary tract of the rat.
In both rodent and primate in vivo models, cholecystokininB (CCKB) antagonists such as PD134,308 have anxiolytic effects that may involve the potentiation of GABAergic transmission. We have investigated this interaction using exogenous application of GABA and whole cell patch recording techniques in neurons of the nucleus of the solitary tract (NTS) in brainstem slice preparations. In the presence of PD143,308 the magnitude of the GABA-evoked decrease in membrane input resistance was enhanced by 41.2 +/- 3.1% and the duration of the response was prolonged by 34.8 +/- 2.2%. Also, PD134, 308 potentiated glycine-evoked decreases in membrane input resistance, increasing the amplitude of the response by 62.8 +/- 4. 85 and prolonging the duration of the response by 23.5 +/- 3.6%. The effect of PD134,308 persisted in the presence of tetrodotoxin, after reversal of the transmembrane gradient of chloride ions and under conditions of exaggerated GABAA receptor desensitization. Our results demonstrate that at least part of the functional link between PD134,308 and the GABAA response occurs postsynaptically.
McLean
H A
HA
Institut Alfred Fessard, Biologie Fonctionnelle du Neurone, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, France.
Champagnat
J
J
Denavit-Saubie
M
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D065101:Chloride Channel Agonists; D004357:Drug Synergism; D004553:Electric Conductivity; D005071:Evoked Potentials / Q000187:drug effects; D005998:Glycine / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D017552:Solitary Nucleus / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D065101:Chloride Channel Agonists; D006727:Hormone Antagonists; D007211:Indoles; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D008536:Meglumine; D005998:Glycine