Reduction of extinction and reinstatement of cocaine seeking by wheel running in female rats - PubMed (original) (raw)

Reduction of extinction and reinstatement of cocaine seeking by wheel running in female rats

Natalie E Zlebnik et al. Psychopharmacology (Berl). 2010 Mar.

Abstract

Rationale and objectives: Previous work has shown that wheel running reduced the maintenance of cocaine self-administration in rats. In the present study, the effect of wheel running on extinction and reinstatement of cocaine seeking was examined. Female rats were trained to run in a wheel during 6-h sessions, and they were then catheterized and placed in an operant conditioning chamber where they did not have access to the wheel but were allowed to self-administer iv cocaine. Subsequently, rats were divided into four groups and were tested on the extinction and reinstatement of cocaine seeking while they had varying access to a wheel in an adjoining compartment. The four groups were assigned to the following wheel access conditions: (1) wheel running during extinction and reinstatement (WER), (2) wheel running during extinction and a locked wheel during reinstatement (WE), (3) locked wheel during extinction and wheel running during reinstatement (WR), and (4) locked wheel during extinction and reinstatement (WL). WE and WR were retested later to examine the effect of one session of wheel access on cocaine-primed reinstatement.

Results: There were no group differences in wheel revolutions, in rate of acquisition of cocaine self-administration, or in responding during maintenance when there was no wheel access. However, during extinction, WE and WER responded less than WR and WL. WR and WER had lower cocaine-primed reinstatement than WE and WL. One session of wheel exposure in WE also suppressed cocaine-primed reinstatement.

Conclusions: Wheel running immediately and effectively reduced cocaine-seeking behavior, but concurrent access to running was necessary. Thus, exercise is a useful and self-sustaining intervention to reduce cocaine-seeking behavior.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

Mean (± SEM) responses (a) and iv 0.4 mg/kg cocaine infusions (b) in groups WR, WER, WE, and WL during daily 6-h self-administration sessions over the 10-day maintenance period. Session blocks 7 to 8 and 9 to 10 (**p<0.01) had significantly more responses (a) and infusions (b) than session blocks 1 to 2 when group data were collapsed and analyzed across five two-session blocks

Fig. 2

Fig. 2

Mean (± SEM) responses (a) and iv saline infusions (b) during daily 6-h self-administration sessions over the 14-day extinction period. Groups WL and WR were combined and then, separately, WER and WE were combined, as they showed no significant differences. Following introduction of the wheel on day 1 of extinction, combined Groups WL+WR exceeded combined Groups WER+WE in responses (a) and infusions (b) on session blocks 1 to 2 (**p<0.01), 3 to 4 (**p<0.01), and 7 to 8, (*p<0.05). The combined groups also differed on responses on sessions 5 to 6 and 7 to 8 (p<0.05) and on infusions on session 5 to 6 (p<0.01)

Fig. 3

Fig. 3

Mean (± SEM) wheel revolutions over the 14-day extinction period for groups WR (filled circles), WER (open circles), and WE (filled triangles) and during the reinstatement period for each saline (S) or cocaine (C) priming injection for groups WR and WER. During analysis, groups WE and WER were combined, as they did not significantly differ during cocaine extinction, and when wheel revolutions were compared on the first day of extinction vs the last day of training (see Table 2), they were significantly higher during extinction (*p<0.05)

Fig. 4

Fig. 4

Mean (± SEM) responses on the previously active lever (a) following priming injections during reinstatement testing in the between-subjects design with ip saline (S) or 5-, 10-, and 15-mg/kg ip injections of cocaine (C), #p<0.01 vs WER, **p<0.01 vs S, @p<0.01 vs WR, +p<0.05 vs WR. The striped bar indicates the first day after termination of wheel running in WE, and &p<0.01 vs all other groups. Mean (± SEM) responses on the previously active lever (b) following priming injections of saline (S) or two 15-mg/kg cocaine (C1, C2) during a within-subjects reinstatement procedure in groups WE and WR (cocaine and wheel access-cross-hatched bar), **p<0.01 vs S, #p<0.01 vs WR, †p<0.05 vs WR, † = 0.05 vs WR, ‡p<0.05 vs C + W, a = p<0.01 vs C +W

References

    1. Ahmad SO, Park JH, Stenho-Bittel L, Lau YS. Effects of endurance exercise on ventral tegmental area neurons in the chronic 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine and probenecid-treated mice. Neurosci Lett. 2009;450:102–105. - PubMed
    1. Ahmadi J, Kampman K, Dackis C. Outcome predictors in cocaine dependence treatment trials. Am J Addict. 2006;15:434–439. - PubMed
    1. Alaei H, Borjeian L, Azizi M, Orian S, Pourshanazari A, Hanninen O. Treadmill running reverses retention deficit induced by morphine. Eur J Pharmacol. 2006;536:138–141. - PubMed
    1. Avena NM. Examining the addictive-like properties of binge eating using an animal model of sugar dependence. Exp Clin Psychopharmacol. 2007;15:481–491. - PubMed
    1. Avena NM, Rada P, Hoebel BG. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 2008;32:20–39. - PMC - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources