Elsevier

Biological Psychiatry

Volume 65, Issue 10, 15 May 2009, Pages 851-856
Biological Psychiatry

Archival Report
High Impulsivity Predicts Relapse to Cocaine-Seeking After Punishment-Induced Abstinence

https://doi.org/10.1016/j.biopsych.2008.12.008Get rights and content

Background

Relapse is a hallmark feature of cocaine addiction and a main challenge for treatment strategies. Human studies indicate a link between impulsivity and increased susceptibility to relapse.

Methods

Rats were screened for high (HI) and low impulsivity (LI) on the 5-choice serial reaction time task. The HI and LI rats were trained to self-administer cocaine under a seeking-taking chained schedule: responses on the seeking lever resulted in presentation of the taking lever, responding upon which resulted in cocaine reinforcement. After the establishment of stable responding, an intermittent punishment schedule was introduced: completion of the seeking link resulted in the random presentation of either the taking lever or a mild footshock. This resulted in a progressive decrease in cocaine-seeking approaching abstinence. Relapse was assessed 7 days after punishment, during which responding on the seeking lever resulted in the presentation of the cocaine-associated stimuli (i.e., in the absence of cocaine or footshock).

Results

The HI and LI animals significantly reinstated the cocaine-seeking response after a single phase of seeking punishment. However, after a second punishment phase only the HI rats reinitiated suppressed seeking responses and relapsed, an effect that was facilitated by prior extended cocaine access. In a preliminary study we found that the selective noradrenaline reuptake inhibitor, atomoxetine, a drug known to reduce impulsivity, prevented the reinstatement of cocaine-seeking.

Conclusions

Impulsivity pre-dating drug abuse increases the susceptibility to relapse after abstinence. Medications targeting impulsivity might have utility as treatment interventions for relapse prevention and the promotion of abstinence.

Section snippets

Animals

Outbred male Lister Hooded rats (Charles River, Margate, United Kingdom) weighing 250–275 g at the beginning of the experiments were used. Rats were housed in groups of four during testing on the 5-CSRTT and were individually housed after intravenous catheterization. Rats were fed at the end of each day's testing and housed under temperature- and humidity-controlled conditions and a reversed 12-hour light/dark cycle (lights off at 7:00 am). All experimental procedures conformed to the UK (1986)

Experiment 1: Relapse to Cocaine-Seeking in HI and LI Rats

The HI (n = 8) and LI (n = 14) animals (Table 1 in Supplement 1) rapidly acquired cocaine self-administration under the seeking-taking chained schedule of reinforcement and to nose-poke into the magazine to obtain sucrose (Figure 1C). At the end of the training phase all animals received similar overall numbers of cocaine infusions and sucrose reinforcement (data not shown). During punishment, 6 HI and 10 LI rats progressively decreased cocaine-seeking [F(7,98) = 51.7; p < .01] (Figure 1A) and

Discussion

The results of the present study show that HI rats have an increased propensity to relapse after abstinence induced by the suppression of drug-seeking responses by intermittent punishment. Whereas LI rats only relapsed after a first but not a second phase of the suppression of drug-seeking by punishment, HI rats readily reinstated their drug-seeking after the second punishment phase, and this tendency was greatly increased after prolonged access to cocaine.

Relapse to compulsive drug use is a

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