We next directly tested whether impulsive SHRs were more vulnerable to heroin addiction using a drug self-administration (SA) task that models different components of the abuse cycle. While lever pressing did not initially differ between the strains, SHRs pressed more on both active (F1,9=18.62, p=0.002. Fig. 1e) and inactive levers (F1,9=5.11, p=0.05, Fig. 1e) during the maintenance phase, and therefore cumulatively consumed more heroin than WKYs (t9=4.31, p=0.002, Fig. 1f). Despite their clear preference for the active lever, SHRs showed diminished motor inhibition evident by greater inactive lever pressing relative WKYs, which is in line with their elevated impulsive action as measured in the ITD task. While differences in inactive lever pressing could represent the strains’ baseline differences in locomotor activity, this does not fully explain the SA data since there was no correlation between inactive lever responses and general locomotion (Supplementary Fig. 3).
