Figure 5. Decreasing OPHN1 levels in VTA DA neurons makes adult mice more susceptible to cocaine-induced LTP.
(a) A low dose of cocaine (5 mg/kg) induced LTP in adult Ophn1-shRNA injected VTA DA neurons (a, Right, p<0.01, n=5, t8=5.464); above representative traces of AMPAR and NMDAR EPSCs (top). (b) Low doses of cocaine (5 mg/kg) induced CPP in mice locally injected with Ophn1-shRNA (p<0.01, n=14, t26=3.600), but not in control mice injected with scrambled shRNA (p=0.7829, n=4, t6=0.2882). (c) Sal003 (20 μM) blocked the cocaine-induced LTP in the VTA of control shRNA-injected mice (p<0.01, n=6/6/7 vehicle/cocaine/cocaine+Sal003, F2,16=13.03), but failed to do so in Ophn1-shRNA VTA DA neurons (p=0.29, n=6/6/11, vehicle/cocaine/cocaine+Sal003, F2,20=4.29, cocaine vs. cocaine+Sal003; p<0.05 vehicle vs. cocaine or cocaine+Sal003). (d) Representative sample traces of AMPAR EPSCs. (e–f) I-V plots. (g) Cocaine increased the rectification index in control-shRNA injected VTA neurons while Sal003 blocked it (p<0.001, n=6/6/7 vehicle/cocaine/cocaine+Sal003, F2,16=30.30, cocaine vs. vehicle or cocaine vs. cocaine+Sal003), whereas both cocaine and cocaine+Sal003 increased the rectification index in VTA DA neurons from Ophn1-shRNA-injected mice (p<0.05, n=6/6/11 vehicle/cocaine/cocaine+Sal003, F2,20=3.92, vehicle vs. cocaine or cocaine+Sal003; p=0.80 cocaine vs. cocaine+Sal003). Plots are mean ± s.e.m.