Figure 1.

Pharmacological and genetic studies indicate that mGlu₃ is the group II mGlu subtype that mediates potentiated cyclic-AMP (cAMP) accumulation. Rat hippocampal slice (a and b) or mouse cortical slice (c–h) cAMP assays were performed in the absence (Vehicle) or presence of either 10 μM isoproterenol (ISO), 100 nM LY379268 (LY), 30 μM VU0469942 (VU), ISO+LY, ISO+LY+10 μM VU, or ISO+LY+30 μM VU. Data are normalized to the fold-over basal cAMP response and represent the mean of at least three independent experiments performed in at least triplicate with error bars representing SEM. *p<0.05 compared with all other conditions except for ISO+LY+10 μM VU. Concentration response curves (CRCs) of LY379268 were performed in rat hippocampal slice (b) or mouse cortical slice (d). cAMP assays in the presence of 10 μM ISO and in the absence or presence of 1 μM (b) or 10 μM (d) BINA. For studies utilizing mGlu₂ and mGlu₃ knockout mice and their wild-type littermates, mouse cortical slice cAMP assays were performed in the absence (Vehicle) or presence of either 10 μM ISO, 100 nM, or 1 μM LY379268 (LY) as indicated, and ISO+LY, or ISO+LY+1 μM MNI-137 (MNI). (e and f) Represent data that were obtained from experiments in WT littermates and data from mGlu₂ and mGlu₃ KO mice are presented in g and h, respectively. Data are normalized to the fold-over basal cAMP response and represent the mean of four independent experiments performed blinded to the genotype in quadruplicate with error bars representing SEM. *p<0.05 compared with all other conditions except for either ISO+LY (100 nM) or ISO+LY (1 μM) where applicable.