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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    816—Cocaine Reinforcement, Seeking, and Reinstatement II

    Wednesday, November 13, 2013, 1:00 pm - 5:00 pm

    816.13: Chronic forced exercise inhibits stress-induced reinstatement of cocaine conditioned place preference in female Sprague Dawley rats

    Location: Halls B-H

    *L. S. ROBISON1,2, L. ALESSI2, J. K. ROBINSON1, B. J. ANDERSON1, N. D. VOLKOW3, P. K. THANOS2,1,3;
    1Psychology, Stony Brook Univ., Stony Brook, NY; 2Behavioral Neuropharm. and Neuroimaging Lab., Brookhaven Natl. Lab., Upton, NY; 3Lab. of Neuroimaging, NIAAA, NIH, Bethesda, MD

    Abstract Body: Background: Stress increases the likelihood of cocaine relapse in both rodents and humans, even following a prolonged extinction/abstinence period. While pharmacological agents that blunt the action of stress pathways can prevent drug cravings and stress-induced relapse, caution must be taken against the development of side effects from such treatment. Moreover, an ideal treatment for cocaine dependence would be one that both attenuates reactivity to stressors and enhances the functioning of the reward pathway. Exercise presents a natural and cost-effective means of accomplishing both of these goals, while having a plethora of other benefits. Exercise has been shown to decrease the likelihood of drug dependence, reduce cravings in humans, and inhibit relapse behaviors due to other risk factors in rodents. The present study aims to evaluate the efficacy of exercise to reduce stress-induced relapse in a rodent model of cocaine dependence. Methods: Eight week old female Sprague Dawley rats were tested for cocaine conditioned place preference (CPP), then split into sedentary (six weeks of no exercise, remained in home cage; n=12) and exercise [six weeks of one hour daily treadmill running (non-shock motivated); n=12] groups. Immediately following the cocaine CPP paradigm (and during the beginning of the exercise/sedentary period), rats were tested for cocaine CPP extinction behavior. Following the six week exercise/sedentary period, rats were tested for cue- and stress- (15 minute restraint) primed reinstatement on subsequent days. Additionally, rats were tested for physiological (serum corticosterone levels) and behavioral (open field activity) responses to stress (15 minute restraint) before and after the entire experiment. Results & Conclusions: Rats in both groups formed a similarly significant preference for cocaine (increase in time spent in cocaine-paired chambert: exercise 36.8%, sedentary 36.3%). Exercise did not affect the number of days to reach extinction criteria (exercise 6.4 +/- 1.6, sedentary 6.8 +/- 1.6 days). Neither group exhibited cue-induced reinstatement, which was expected following extinction. While sedentary rats showed significant stress-induced reinstatement of cocaine CPP, this was inhibited in exercise treated rats. Exercise attenuated time spent in the cocaine-paired chamber following stress by 28.4% compared to sedentary rats. In addition, exercise altered stress-induced behavioral responses in the open field, and corticosterone responses are currently being analyzed and will be presented at the meeting. This study suggests that exercise may be an effective means of preventing stress-induced relapse.

    Lay Language Summary: Our research indicates that long-term aerobic exercise may be capable of protecting against relapses of cocaine abuse triggered by stress.
    Cocaine is a highly addictive substance, and addiction to this drug poses a major problem in the United States. Cocaine abuse results in nearly a half million hospitalizations per year, and is linked with rising health care and social welfare costs, low workforce productivity, and increased crime and unemployment rates. Over one million Americans currently meet criteria for dependence or abuse of cocaine. Although many cocaine-dependent individuals seek out treatment, dropout rates for these treatment programs often reach 30% or higher, and despite attempts to remain abstinent, one- to two- thirds of individuals who complete treatment programs report relapsing within just a few months after discharge.
    Stress and negative affect associated with withdrawal are major factors leading to relapse, which has been demonstrated in both human and non-human animals. This is believed to be due to the interaction between the brain’s stress and reward pathways. An ideal treatment for cocaine dependence would be one that both reduces reactivity to stressors and improves the functioning of the reward pathway. Exercise presents a natural and cost-effective means of accomplishing both of these, while having a plethora of other beneficial effects on the brain, mind, and body. Previously, exercise has been shown to decrease the likelihood of drug dependence, while also curbing cravings in humans and inhibiting relapse behaviors due to other relapse risk factors in animals.
    In this study, rats were conditioned to associate receiving cocaine with a certain environment, and were later tested for their preference for that environment, which is interpreted as preference for the drug itself. As expected, rats had a strong preference for cocaine. Rats were then split into two groups, the exercise group and the sedentary group. Exercise rats ran on a motorized treadmill for one hour per day for six weeks. The sedentary group did not exercise. At the end of this six week exercise or sedentary period, rats were subjected to a stressor, and relapse for preference of the drug was measured. While sedentary animals showed a strong relapse for cocaine preference due to stress exposure, this was blocked in animals that had previously exercised.
    These results suggest that exercise may affect the brain’s stress and/or reward pathway, resulting in these alterations in behavior. We are currently in the process of analyzing blood samples that were taken from these animals at baseline and in response to stress to determine whether these differences in behavior could be attributable to exercise reducing hormonal responses to stressful events. The next step of this research is to delve deeper into the underlying mechanisms of our findings by using a variety of neurochemical assays and brain imaging techniques such as positron emission tomography (PET).
    The findings from this study provide promise for using exercise as an effective means of battling cocaine addiction and preventing relapse. These results add to those from previous studies that have also found that exercise is effective in preventing drug cravings and addictive behaviors, as well as preventing relapse due to other triggers.