THE GAMMA-AMINOBUTYRIC-ACID UPTAKE INHIBITOR NO-711 POTENTIATES 3-AMINOPROPYLPHOSPHINIC ACID-INDUCED ACTIONS IN RAT NEOCORTICAL SLICES

In rat neocortical slices maintained in Mg2+-free Krebs medium, the GA BA(B) receptor agonists baclofen and 3-aminopropylphosphinic acid dose -dependently reduced the frequency of spontaneous discharges, 3-aminop ropylphosphinic acid being 10 times less potent than baclofen. These w ere sensitive to the antagonist CGP 52432 henyl)methyl]-amino](-P-diet hoxymethyl)-phosphinic acid) (1, 5 and 10 mu M). The GABA uptake inhib itor NO-711 (1-(2-(((diphenylmethylene)amino)oxy)ethyl- 1,2,5,6-tetrah ydro-3-pyridinecarboxylic acid) (5 and 10 mu M) produced 2.9 and 9 fol d increases in the potency of 3-aminopropylphosphinic acid without aff ecting baclofen-induced responses. In this study, the low potency of 3 -aminopropylphosphinic acid when compared to baclofen, may be attribut ed to its uptake by NO-711-sensitive GABA transporters. (C) 1998 Elsev ier Science B.V.