Modafinil reinstates a cocaine conditioned place preference following extinction in rats

Abstract

The current study examined whether modafinil would reinstate an extinguished cocaine conditioned place preference (CPP). Following extinction of a cocaine CPP, rats were administered modafinil (128 mg/kg), cocaine (5 mg/kg) or vehicle and given a 60-min reinstatement test. While the effect of cocaine was transient, modafinil robustly reinstated a cocaine CPP following extinction, suggesting that modafinil may induce relapse or increase the vulnerability of addicts to the reinforcing effects of environmental triggers.

Figure 1

CPP during Test 1 and Test 5. (A) Cocaine induced a CPP following conditioning. Data represent mean (+SEM) time spent on GRID floor for the GRID+ and GRID− subgroups during the first 15 min of the 25-min drug-free test. All groups showed a significant preference for the cocaine-paired floor. (B) Cocaine CPP was absent following extinction. Data represent mean (+SEM) time spent on GRID floor for the GRID+ and GRID− subgroups during the first 15 min of the 25-min drug-free test. All groups demonstrated extinction of preference, failing to show a preference for the cocaine-paired floor. VEH=Vehicle, COC=Cocaine, MOD=Modafinil; *p < .017(Bonferroni-corrected α/3), **p < .001.

Figure 2

Modafinil- and cocaine-induced reinstatement of an extinguished cocaine CPP during the first 15-min interval of the 60-min reinstatement test. (A) Modafinil- and cocaine-treated rats show a significant reinstatement of preference. Data represent mean (+SEM) time spent on GRID floor for the GRID+ and GRID− subgroups during the first 15 min of the 60-min test. Rats that received modafinil or cocaine showed a significant cocaine CPP during the 15-min interval, while vehicle-treated rats failed to show a preference. (B) Activity levels during the first 15-min interval. Data represent mean (+SEM) activity counts during the first 15 min of the 60-min test. Modafinil- and cocaine-treated rats show significantly higher activity than vehicle-treated rats. VEH=Vehicle, COC=Cocaine, MOD=Modafinil; *p < .017(Bonferroni-corrected α/3), **p < .001, ^ap < .001(vs. VEH), ^bp < .005(vs. VEH).

Figure 3

Modafinil-induced reinstatement of an extinguished cocaine CPP during the last 15-min interval of the 60-min test. (A) Modafinil-treated rats show a significant reinstatement of preference. Data represent mean (+SEM) time spent on GRID floor for the GRID+ and GRID− subgroups during the last 15 min of the 60-min test. Rats that received modafinil showed a significant cocaine CPP during the 15-min interval, while vehicle- and cocaine-treated rats failed to show a preference. (B) Activity levels during the last 15-min interval. Data represent mean (+SEM) activity counts during the last 15 min of the 60-min test. Modafinil-treated rats show significantly higher activity than vehicle- or cocaine-treated rats. VEH=Vehicle, COC=Cocaine, MOD=Modafinil; *p < .005(Bonferroni-corrected α/3 = .017), ^ap < .001(vs. VEH/COC).