Figure 1. Impact of tonic cGMP signaling on corticostriatal synaptic transmission in vivo.

(a) Recording arrangement employed to study the pharmacological effects of the sGC inhibitor ODQ on corticostriatal transmission in vivo (see Methods section for details). Cortically-evoked postsynaptic potentials (PSPs) were recorded by means of local field potential (LFP) recordings. Inset shows examples of traces of corticostriatal PSPs (calibration bars: 30 ms, 1 µV). (b) Time course of corticostriatal PSPs recorded before and following systemic administration of 10 mg/kg and 20 mg/kg ODQ (i.p., n = 5 rats per dose). A marked attenuation of the corticostriatal response was observed following 20 mg/kg ODQ, an effect that becomes apparent after 20 min of drug administration. (c) Time course of corticostriatal PSPs recorded before and following 20 mg/kg ODQ + intrastriatal administration (0.1 µl/min×10 min) of the cGMP analog 8-Br-cGMP (20 mM; n = 5 rats) or vehicle (aCSF; n = 5 rats). Note that the characteristic attenuation of corticostriatal PSPs observed after 20 min of 20 mg/kg ODQ administration was lacking following intrastriatal infusion of 8-Br-cGMP. (d) Bar graph depicting the averaged changes in PSP responses obtained from the last 3 data points shown in c (marked in gray). Intrastriatal infusion of 8-Br-cGMP completely blocked the effects of ODQ (***P<0.0005, unpaired t-Test).