Following training to self-administer heroin, animals were placed into daily NAC (n= 24) or vehicle (n= 23) treatment groups to begin extinction training. The average number of active lever presses over the last 3 days of self-administration training was equivalent between the groups (NAC= 62 ± 17; vehicle= 58 ± 14, mean±sem). illustrates that NAC (100 mg/kg, ip) significantly augmented the extinction of active lever pressing compared to vehicle pretreated subjects; an effect most apparent during the first 5 days of extinction training (). A two-way ANOVA with repeated measures over 7 days of extinction revealed a significant effect of NAC (F(1,270)= 9.23, p= 0.004) and withdrawal time (F(6,270)= 16.71, p< 0.001), but no treatment x time interaction. The first day of extinction was analyzed in hourly intervals, and the primary inhibitory effect of NAC on extinction lever pressing was during the first h (). After 7 days of extinction training daily NAC and vehicle treatment groups showed equivalent levels active lever pressing (NAC= 12 ± 4; vehicle 16 ± 4).
Daily NAC administration facilitates extinction training and produces enduring inhibition of cue- and heroin-induced reinstatement
On day 11 animals were pretreated with NAC or vehicle and 2.5 h later underwent a cue-induced reinstatement trial. illustrates that cue-induced reinstatement was significantly blunted by NAC (Student’s t(45)= 3.089, p= 0.003). Animals were then administered NAC or vehicle daily in the home cage for 3 days. The next day (day 15) at 2.5 h after NAC or vehicle pretreatment, all rats were injected with heroin (0.25 mg/kg, sc) in the operant chamber. NAC pretreated animals showed less heroin-induced reinstatement than vehicle pretreated subjects (Student’s t(45)= 2.569, p= 0.014). Akin to the first day of extinction training, the inhibitory effect of NAC was predominant in the first h of the cue and heroin reinstatement trials (data not shown).
Following the heroin reinstatement trial on day 15 (), animals were placed in the home cage for an additional 40 days without receiving injections of NAC, vehicle or heroin. shows that after 40 days of abstinence, cue-induced reinstatement remained significantly blunted in animals that had been previously pretreated with daily NAC on days 1 through 15 (Student’s t(39)= 3.075, p= 0.004). Similarly, after another 3 days in the home cage, animals were administered a heroin priming injection in the operant chamber and those previously pretreated with daily NAC showed significantly less reinstatement relative to control subjects (Student’s t(39)= 3.733, p< 0.001).
illustrates that inactive lever pressing during all reinstatement trials were equivalent between the NAC and vehicle treatment group. shows that chronic pretreatment with NAC did not alter the motor response elicited by placing a rat in an open field. Although this experiment indicates that chronic NAC was not inducing overt inhibition of motivated behavior, it remains possible that operant behaviors could be nonspecifically suppressed by NAC.