After stable maintenance, animals underwent an extinction phase at which time responses on the previously reinforced lever resulted in saline delivery, not heroin. As expected, lever pressing decreased over time in both strains (F16,128=10.27, p<0.001, Fig. 1g), yet as evident by non-linear regression, SHRs extinguished at a slower rate (k parameter: t32=2.84, p=0.008) and to a lesser extent (plateau parameter: t32=3.41, p=0.002). Following extinction, reinstatement liability was determined by exposing the animals to a non-extinguished cue previously associated with heroin delivery. The drug-associated cue promoted heroin seeking behavior in both strains (F1,8=37.61, p<0.001), but SHRs exhibited enhanced heroin seeking with a larger number of active lever presses than WKY (t8=2.64, p=0.03, Fig. 1h). Overall, these results demonstrate that SHRs have greater dopamine sensitivity to heroin, maintain higher levels of heroin intake, exhibit decreased capacity to extinguish their drug intake, and have a greater tendency for relapse, all supporting the hypothesis of enhanced drug addiction sensitivity associated with the impulsive phenotype.
