[en] Full text: GABA_C (γ-aminobutyric acid) receptors are characterised by their insensitivity to the GABA_A-selective antagonist, bicuculline and the GABA_B-selective agonist, baclofen. These receptors are composed of a homo- or hetero-oligomeric assembly of novel subunits termed ρ₁ and ρ₂. The subunit ρ₁ is located mainly in the retina, although it has been identified in Purkinje cells of the cerebellum, whilst ρ₂ is more widely expressed in the CNS (cerebellum, hippocampus and cortex). The functional role of these receptors has yet to be established. They may be involved in the regulation of the sleep-wake cycle, modulation of excitatory neurotransmitter release and in the inhibition of pre-synaptic calcium currents. The present study investigated the potential role of GABA_C receptors in guinea pig cerebellar tissue slice metabolism by analysing the fate of ¹³C from [3-¹³C]pyruvate by NMR spectroscopy, in the absence (control) and presence (20 μM) of the GABA_C selective antagonist, (1,2,5,6-tetrahydropyridin-4-yl)methyl-phosphonic acid TPMPA). Net flux and fractional enrichment of Glu, GABA, Gln, Ala and Asp isotopomers was measured by NMR spectroscopy and the rate of efflux of amino acids into the buffer was estimated by HPLC. Net flux of ¹³C into Glu C3 and C4 significantly increased, but release of Glu into the buffer was decreased by TPMPA. There was no increase of net flux into Gln C4, and net flux into Ala C3 was decreased. These data suggest that TPMPA-sensitive GABA_C receptors influence the release of neurotransmitter glutamate in the cerebellum