GABAB receptor antagonist CGP-36742 enhances somatostatin release in the rat hippocampus in vivo and in vitro

Here, we show the modulation of somatostatin functions in the hippocampus by the orally active 'cognition enhancer' GABA(B) receptor antagonist, (3-aminopropyl)n-butylphosphinic acid (CGP-36742), both in vivo and in vitro. Using high-pressure liquid chromatography-coupled electrospray mass spectrometry, we measured a two-fold increase in the extracellular level of somatostatin to CGP-36742 application in the hippocampus of anaesthetised rats. The basal release of[I-125] somatostatin in the synaptosomal fraction was increased by CGP-36742 in concentrations lower than 1 muM. Simultaneous measurement of [C-14]Glu and [H-3]gamma-aminobutyric-acid ([H-3]GABA) showed that CGP-36742 increased their basal release. However, prior [I-125] somatostatin application suppressed the increase in the basal release of [C-14]Glu and induced a net decrease in the basal release of [H-3]GABA. Somatostatin application had a similar effect. In slices, CGP-36742 increased the postsynaptic effect of somatostatin on CA1 pyramidal cells. These results suggest a pre- and postsynaptic functional 'cross-talk' between coexisting GABAB and somatostatin receptors in the rat hippocampus. (C) 2003 Elsevier B.V. All rights reserved.