D2Rs provoke GABAAR-dependent paradoxical responses following PCE. (A) In MSNs from SPF mice, representative traces (above) and graph demonstrate that the D2R agonist quinpirole reduces the amplitude of the first eEPSC (in each pair; −160±27 pA for vehicle vs. −140±29 pA following quinpirole) and increases the PPR (1.2±0.1 in vehicle to 1.6±0.2 in quinpirole). (B) In MSNs from cocaine mice, quinpirole increased the amplitude of the first eEPSC (−81±18 pA for vehicle vs. −106±20 pA for quinpirole) and the PPR decreased (1.4±0.2 in vehicle vs. 1.0±0.1 in quinpirole). (C) In MSNs from SPF mice, quinpirole diminished the frequency (inset, left; 5.1±0.9 Hz in Veh vs. 4.1±0.8 Hz in quinpirole), but not amplitude (inset, right) of low-release probability (5–10 pA) inward currents. For panels C and D, #p<0.05, ##p<0.01, paired t-test. (D) In MSNs from cocaine-exposed mice, quinpirole increased the frequency (3.4±0.7 Hz in Veh vs. 4.7±1 Hz in quinpirole) of low-release probability mEPSCs, while having no effect on the cumulative amplitude distribution. (E) Amphetamine (left) and quinpirole (right) decreased FM1-43 destaining in slices from saline and SPF mice, but increased release in slices from cocaine mice. *p<0.05, **p<0.01, Mann-Whitney. (F) In cells from SPF mice, the GABABR antagonist CGP52432 did not change the eEPSC amplitude (−132±20 pA for Veh vs. −122±16 pA for CGP52432) or the PPR (1.3±0.1 in Veh vs. 1.4±0.1 in CGP52432). When quinpirole was added to CGP52432, the eEPSC amplitude decreased (−115±15 pA) and the PPR increased (1.6±0.1). (G) In MSNs from cocaine-exposed mice, the GABABR antagonist increased the eEPSC amplitude (−94±23 pA for Veh vs. −121±26 pA for CGP52432) and decreased the PPR (1.5±0.1 in Veh vs. 1.0±0.1 in CGP52432). When quinpirole was added to CGP52432, there was a slight reduction in eEPSC amplitude (−112±12 pA) and an increase in the PPR (1.3±0.1). (H) In MSNs from SPF mice, bicuculline did not change the amplitude of the first evoked current (−143±31 pA for Veh vs. −148±33 pA for bicuculline; p=0.1) or the PPR (1.1±0.1 in Veh vs. 1.2±0.2 in bicuculline; p=0.06, paired t-test). When quinpirole was added to bicuculline, the eEPSC amplitude decreased (−132±22 pA) and the PPR increased (1.5±0.1). (I) In MSNs from cocaine mice, bicuculline did not change the amplitude of the eEPSC (−103±24 pA for Veh vs. −101±21 pA for bicuculline) or the PPR (0.9±0.1 in Veh vs. 0.9±0.1 in bicuculline). When quinpirole was added to bicuculline, the eEPSC amplitude decreased (−82±21 pA) and the PPR increased (1.3±0.1). Bars: A, B, F, and G–I, 100 pA, 12.5 ms; C and D, 10 pA, 250 ms.