Group III metabotropic glutamate receptors act as hetero-receptors modulating evoked GABA release in the globus pallidus in vivo

In vitro studies suggest that group III metabotropic glutamate (mGlu) receptors function as hetero-receptors to modulate GABA release within the globus pallidus. In the present study we examined this hypothesis in vivo, using microdialysis to assess the ability of locally infused group III mGlu receptor agonists to modulate KCl-evoked GABA release in the globus pallidus of anaesthetised rats. Extra-cellular levels of GABA in dialysate samples were assayed using High Pressure Liquid Chromatography (HPLC) coupled to electrochemical detection. Infusion of KCl (50–100 mM) evoked a dose-dependent increase in GABA levels in the globus pallidus. Addition of the group III mGlu receptor agonists l-AP4 (30 and 300 μM) and l-SOP (3–300 μM) significantly reduced the extra-synaptic levels of GABA that resulted after 100 mM KCl challenge. The effect of l-SOP (30 μM) was almost totally abolished by co-infusion with M-SOP (30 μM). These data confirm that activation of group III mGlu receptors inhibits GABA release in the globus pallidus, thereby supporting their hetero-receptor role in vivo.