Unidirectional relationship between heroin self-administration and impulsive decision-making in rats

Abstract

Rationale: There is growing clinical evidence for a strong relationship between drug addiction and impulsivity. However, it is not fully clear whether impulsivity is a pre-existing trait or a consequence of drug abuse. Recent observations in the animal models show that pre-existing levels of impulsivity predict cocaine and nicotine seeking. Whether such relationships also exist with respect to non-stimulant drugs is largely unknown.

Objective: We studied the relationship between impulsive choice and vulnerability to heroin taking and seeking.

Materials and methods: Rats were selected in the delayed reward task based on individual differences in impulsive choice. Subsequently, heroin intravenous self-administration behaviour was analysed, including acquisition of heroin intake, motivation, extinction and drug- and cue-induced reinstatement. Throughout the entire experiment, changes in impulsive choice were monitored weekly.

Results and discussion: High impulsivity did not predict measures of heroin taking. Moreover, high impulsive rats did not differ from low impulsive rats in extinction rates or heroin- and cue-induced reinstatement. However, both groups became more impulsive as heroin self-administration continued. During abstinence, impulsivity levels returned towards baseline (pre-heroin) levels. Our results indicate that, in contrast to psychostimulants, impulsive choice does not predict vulnerability to heroin seeking and taking.

Conclusion: These data implicate that different neural mechanisms may underlie the vulnerability to opiate and psychostimulant dependence. Moreover, our data suggest that elevated impulsivity levels as observed in heroin-dependent subjects are a consequence of heroin intake rather than a pre-existing vulnerability trait.

Fig. 1

Schematic diagram showing the experimental design of the present study. HI high impulsive, LI low impulsive

Fig. 2

Selection of high impulsive (HI) and low impulsive (LI) rats, based on their indifference points, calculated as an average of the last 4 days of a stable baseline period on the delayed reward task. HI had a significant lower preference for the large reward compared to LI on all but the 0 s delay. HI high impulsive (n = 13), LI low impulsive (n = 12). *p < 0.001

Fig. 3

a Number of active and inactive lever presses for heroin during 150 min self-administration sessions on FR1, FR2 and FR4 schedule for HI and LI. b Total number of active and inactive lever presses during a progressive ratio schedule of heroine reinforcement in HI and LI rats

Fig. 4

a Number of active and inactive lever presses during the extinction of heroine self-administration in HI and LI rats. b Number of total active and inactive lever presses during 60 min of cue-induced and 60 min of drug-induced reinstatement, compared to the average of the last three extinction sessions for HI and LI

Fig. 5

Indifference point as indication of impulsive behaviour as an average of the last 4 days of baseline, 3 days of stable baseline after IV canulation, during FR1, FR2, FR4, progressive ratio, extinction and the average of the last 3 days after 5 weeks of abstinence. Data are shown for HI and LI, expressed as a absolute data and b percentage of baseline. *HI vs LI p < 0.001; #FR2 vs baseline, after surgery, extinction; $PR vs baseline, after surgery, extinction, abstinence p < 0.05