Abstract

Studies in humans suggest that exposure to stress is related to relapse to tobacco use. The reinstatement of conditioned place preference (CPP) provides a simple, noninvasive and easy approach to investigate the mechanisms for drug relapse. The present study investigated whether repeated exposure to stress could change the extinction and reinstatement of nicotine-induced CPP. Adult male Wistar were exposed to restraint-stress for 2 hours/daily for 7 days, while the control-group was left undisturbed during this period. One day after the last stress session the CPP protocol was carried out. Nicotine produced a place preference to the compartment paired with its injections during conditioning (.16 mg/kg, s.c.; four drug sessions). Once established, nicotine place preference was extinguished by alternate exposure to each compartment after a saline injection (four exposures to each compartment). The animals that did not show extinction of CPP were submitted to two other extinction sessions. Following this extinction phase, the reinstatement of place conditioning was investigated following a priming injection of nicotine. Both control and stress groups showed reinstatement of CPP. The percentage of rats from the stress group that extinguished nicotine-CPP in the first and second test was lower as compared to the control group. In conclusion, stress delayed the extinction of the nicotine-induced CPP, but did not modify the reinstatement.

Highlights

  • According to the World Health Organization, cigarette smoking is the leading cause of preventable death worldwide (World Health Organization, 2009)

  • The F-Test revealed an increase in the time spent in nicotine–paired compartment in the TEST when compared to PRETEST (F1,52 = 32.86; p < .001), indicating that nicotine induced conditioned place preference (CPP)

  • The χ22 test showed that the percentage of animals that extinguished nicotine-induced CPP in the first and second extinction tests was lower in the stress group as compared to the control one (p < .01) (Table 1)

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Summary

Introduction

According to the World Health Organization, cigarette smoking is the leading cause of preventable death worldwide (World Health Organization, 2009). Tobacco addiction is associated with high rates of relapse to drug use even after prolonged periods of abstinence (Shalev, Grimm & Shaham, 2002; Fiore, 2000). Clinical studies have demonstrated that exposure to stress or the presentation of stress-related imagery can induce relapse to drug seeking in humans Several studies have shown that stress exposure reinstates opioid-, cocaine-, and nicotine-induced CPP (Will et al, 1998, 2004; Der-Avakian et al, 2005; DerAvakian et al, 2006; Leão, Cruz & Planeta, 2009). Despite the strong influence of stress on relapse to tobacco use, the effects of prior exposure to repeated stress on extinction and reinstatement of nicotine-induced CPP has not been investigated. The present study investigated whether repeated stress exposure affects the extinction and reinstatement of nicotine-induced CPP

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