Fig. 4.

Activation of CB₂Rs reduces VTA DA neuronal firing ex vivo. (A) Phase-photo image showing a dissociated VTA DA neuron. (B and C) Representative recording and summarized data illustrating that JWH133 and additional four CB₂R agonists (GW405833, SER601, CB65, and HU308) inhibited VTA DA neuronal firing similarly in WT mice, but not in Zimmer CB₂^−/− mice. This inhibitory effect was blocked by coadministration of AM630 (1 μM). (D and E) Representative AP traces and summarized group data illustrating that JWH133 altered membrane potential (MP), AP firing rate, AP initiation, AP duration, and AHP in WT mice. (F and G) Representative depolarizing current-induced AP firing and summarized data illustrating that JWH133 decreased VTA DA neuronal excitability. (H and I) Representative records and summarized data illustrating that JWH133 or GW405833 (GW) inhibited VTA DA neuronal firing in brain slices in a concentration-dependent manner. This effect was blocked by coadministration of AM630 and was absent in CB₂^−/− mice. All quantificated data are normalized to control (predrug baseline). Error bars indicate ± SEM. *P < 0.05; **P < 0.01, compared with predrug controls. Also see Fig. S6.