Figure 4.
Endocannabinoid-mediated inhibition of GABA release involves intracellular Ca2+ and is initiated by blockade of presynaptic mGluR-IIIs. A1, Mean time courses during bath application of AM251, CGP, and LY. The AM251-induced increase in GABAB IPSC amplitude after mGluR antagonist treatment was prevented by substituting BAPTA for EGTA in the recording solution. A2, Summary of the AM251-induced change in GABAB IPSC amplitude with EGTA or BAPTA. The number of data points is indicated. p < 0.001; t test. All experiments were conducted in the presence of apamin (100 nm) and LY341495 (200 μm). B1, Individual time courses showing the AM251-induced increased in GABAB IPSCs during application of UBP1112 (UBP), a selective mGluR-III antagonist. For comparison, an additional time course for AM251 plus APA is also shown. B2, Averaged IPSC traces collected before and during AM251, as shown in B1. Calibration is identical in both traces. C, Mean time courses illustrating the AM251-induced increase in GABAB IPSCs during UBP1112 treatment. D, Summary of the effects of mGluR antagonists of various classes on the AM251-induced increase in GABAB IPSCs recorded in VTA DA neurons. The nonselective mGluR antagonists include LY341495 (LY2, 200 μm), the mGluR-I selective antagonist CPCCOET (CPC, 100 μm) and MPEP (30 μm), the mGluR-II selective antagonist LY341495 (LY5, 500 nm), and EGlu (200 μm). In all instances, apamin treatment occurred before mGluR antagonist application. **p < 0.01 versus control; one-way ANOVA and post hoc Newman-Keuls comparison.