Fig. 10.

Determination of the role of synaptic and intrinsic mechanisms in JWH133-induced reduction of VTA DA neuronal excitability. (a) Bar graph summarizes data that showed the alteration of AP firing rate before and after JWH133 exposure. The VTA DA neuron AP firing was recorded using cell-attach recording mode in the presence (a) and absence (b) of and of cocktail pharmacology (NBQX+APV + PTX) to block synaptic transmission. (c) Representative typical traces showing the AP firing measured by whole-cell recordings in current-clamp mode before (left) and after (right) JWH133 exposure. In these experiments, the GDP-βS (600 μM) was added into recording electrode, and converted to whole-cell recording mode allowed GDP-βS infusion into recorded cells, and data showed that JWH133 failed to alter AP firing rate. (d) Representative typical traces in control group showing the AP firing measured by whole-cell recordings in current-clamp mode before (left) and after (right) JWH133 exposure without GDP-βS in the pipette solution and showed that JWH133 reduced AP firing rate. (e)/(f) Bar graph summarizes pooled data from (c) and (d) demonstrating that JWH133 significantly reduced AP firing rate in control (d), but not GDP-βS-treated neurons (c). ** p < 0.01, *** p < 0.001, compared to AP firing before JWH133 exposure.