Elsevier

Biological Psychiatry

Volume 68, Issue 3, 1 August 2010, Pages 303-305
Biological Psychiatry

Brief Report
Persistent Increases in Cocaine-Seeking Behavior After Acute Exposure to Cold Swim Stress

https://doi.org/10.1016/j.biopsych.2010.03.030Get rights and content

Background

Acute and chronic stress reinstates drug-seeking behavior. Current animal models show that these effects are contingent (temporally, contextually, or both) on the drug-conditioning environment. To date, no paradigm exists to model the common human situation in which stressors that are distinct from the experience of drugs can lead to relapse.

Methods

Rats were allowed to self-administer cocaine or saline over 8 days. They then underwent extinction training, during which responding was not reinforced with drug infusions. After 16 days of extinction, rats were submitted to a brief cold swim stress and then tested for seeking behavior (responding not reinforced with drug infusions) for 4 days.

Results

All rats developed self-administration behavior. Following extinction, cold swim stress induced reinstatement of drug-seeking behavior in cocaine-trained rats, an effect that was still present 3 days after stress exposure.

Conclusions

This study indicates that cold swim stress can have long-term effects on drug-seeking behavior and may provide us with a suitable model to study the latent effects of stress on relapse to drug abuse.

Section snippets

Methods and Materials

Procedures are described in detail in Supplement 1. Briefly, rats self-administered saline (n = 19) or cocaine (600 μg/kg/infusion, n = 23) using nose pokes as the operant response. After eight self-administration sessions, rats underwent an extinction phase. During extinction, rats were placed in the self-administration chambers for 16 additional sessions during which nose-poking in the active hole did not result in drug delivery. Rats that did not reach the extinction criteria were eliminated

Self-Administration Training and Extinction Phase

All rats nose-poked preferentially in the active hole versus the inactive hole to obtain infusions of either cocaine or saline [hole effect F(1,33) = 61.5, p < .001]. Average daily intake of cocaine was 35 ± 1.4 infusions (i.e., 21 mg/kg/day), whereas it was 8.1 ± 1.4 for saline [drug effect F(1,33) = 163.3, p < .001]. As expected, active/inactive hole discrimination was greater in the cocaine versus saline group [drug × hole interaction F(1,33) = 35.6, p < .001]. In addition, rats with access

Discussion

Our results demonstrate that a brief stressor administered outside the self-administration environment is able to reinstate extinguished cocaine-seeking behavior after the stress itself has ended. This is the first time, to our knowledge, that a stressor both temporally and contextually separated from the drug-paired environment has been shown to induce reinstatement. The effects of cold swim stress on drug-seeking behavior persisted for up to 3 days after exposure to the stress. Swim stress

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