CB1 receptor activation decreases basal synaptic transmission and increases PPR in rat corticostriatal afferents, which is attenuated or prevented by the A2A receptor agonist CGS21680 (30 nM). (A) The whole-cell patch-clamp configuration in horizontal corticostriatal slices from 15–22-day-old rats, with stimulation in the layer V of the adjacent neocortex and recording in the dorsolateral striatum. (B, C) Representative paired-pulse traces (25 ms interpulse interval) in the presence of WIN55212-2 (500 nM) and its vehicle, DMSO. (D) Bar graphs representing the EPSC amplitude values normalized to the pretreatment period after 5 and 16 min of WIN55212-2 perfusion. WIN55212-2 decreased EPSC amplitude at both time points, which was sensitive to AM251, which per se had no effect. Ten minutes of pretreatment with CGS21680 attenuated the CB1 receptor-mediated inhibition of EPSC amplitudes. CGS21680 did not produce effects on its own. All bars are mean ± SEM derived from n ≥ 6 animals. *P < 0.05 versus 100% (pretreatment CTRL). (E) Bar graphs representing the normalized PPR (the second response in relation to the first response) at 5 and 16 min after the beginning of WIN55212-2 perfusion. The WIN55212-2-induced increase (*P < 0.05) in the PPR was prevented both by AM251 and CGS21680, which had no effects per se.