Fig. 4.

Defect of morphine-induced dopamine release in tPA^-/- mice and plg^-/- mice. (A) Basal levels of dopamine in the NAcc did not differ between wild-type and tPA^-/- mice (wild-type, 0.41 ± 0.13 nM, n = 4; tPA^-/-, 0.53 ± 0.01 nM, n = 4). Morphine (10 mg/kg s.c.)-induced dopamine release was markedly diminished in tPA^-/- mice [F_{(1, 6)} = 13.061, P < 0.05]. (B) Basal levels of dopamine in the NAcc of plg^-/- mice did not differ from those in wild-type mice (wild-type, 0.38 ± 0.10 nM, n = 6; plg^-/-, 0.38 ± 0.05 nM, n = 6). Morphine-induced dopamine release in the NAcc was significantly reduced in plg^-/- mice compared to wild-type mice [F_{(1, 10)} = 25.147, P < 0.01]. (C and D) Effect of tPA on dopamine release in the NAcc of tPA^-/- mice. Microinjection of tPA significantly increased basal levels of extracellular dopamine [F_{(1, 8)} = 7.941, P < 0.05] and morphine-induced dopamine release [F_{(1, 8)} = 5.428, P < 0.05) in tPA^-/- mice]. (E and F) Effect of plasmin on dopamine release in the NAcc of tPA^-/- mice. Microinjection of plasmin significantly increased basal levels of extracellular dopamine [F_{(1, 8)} = 6.612, P < 0.05] and morphine-induced dopamine release [F_{(1, 8)} = 13.121, P < 0.01] in tPA^-/- mice. Values indicate means ± SE (n = 4 for A, n = 6 for B, and n = 5 for 4 C-F).