CS-2574

SKF-83566 (0.1 μM-10 μM) causes a concentration-dependent increase in peak evoked extracellular DA concentration ([DA] _o ) evoked by single-pulse stimulation, with a maximum 65% increase in peak evoked [DA] _o with 5 μM. The EC ₅₀ value of this effect of SKF-83566 is 1.3 μM.SKF-83566 inhibited [ ³ H]DA uptake with an IC ₅₀ of 5.73 μM. Moreover, SKF-83566 more potently inhibits the binding of [ ³ H]CFT, a cocaine analog, with an IC ₅₀ of 0.51 μM in [ ³ H]DA uptake and [ ³ H]CFT binding studies.Similarly, in LLc-PK-rDAT cell, SKF-83566 also inhibits [ ³ H]CFT binding with an IC ₅₀ of 0.77 μM in LLc-PK-rDAT cell membrane preparations.

SKF 83566 hydrobromide (oral administration; 20 µg/mL; 7 days) alone has no effects on altering LTP (115%). However, combinnation of SKF 83566 and nicotine significantly blocks the enhancement of long-term synaptic potentiation (LTP) induced by pretreatment with nicotine (SKF 83566+nicotine+cocaine, 120%; nicotine+cocaine, 143%).