Weak effects of local and systemic administration of the GABA uptake inhibitor, SK and F 89976, on extracellular GABA in the rat striatum

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1992-05, Vol.345 (5), p.544-547
• Main Authors: Waldmeier, P C, Stoecklin, K, Feldtrauer, J J
• Format: Article
• Language: English
• ISSN: 0028-1298

The effects of local and systemic administration of the potent GABA uptake inhibitor, SK&F 89976, on GABA overflow from the striatum of conscious rats were investigated in brain dialysis experiments. Administration of the compound via the dialysis probe at concentrations of 25 or 100 mu mol/l significantly increased basal GABA overflow about 2-fold. Overflow evoked by 104 mmol/l K super(+) remained unaltered at the lower and was almost doubled at the higher concentrations; this increase did, however, not reach statistical significance. Given systemically at 50 mg/kg i.p., a dose which is severalfold higher than those which exhibit anticonvulsant effect, SK&F 89976 caused a significant enhancement of K super(+)-stimulated GABA overflow by about a factor of 2; the lower dose of 20 mg/kg i.p. was not effective. Basal GABA overflow was not significantly increased by either dose. These results suggest that the marked effects of nipecotic acid on basal GABA overflow reported by several authors seem to be related to GABA displacement rather than uptake inhibition, and that uptake inhibition does not improve the interpretability of measurements of GABA release by brain dialysis.