Effects of the combination of wheel running and atomoxetine on cue- and cocaine-primed reinstatement in rats selected for high or low impulsivity

Natalie E. Zlebnik, Marilyn E Carroll

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background: Aerobic exercise and the attention-deficit/hyperactivity disorder medication, atomoxetine (ATO), are two monotherapies that have been shown to suppress reinstatement of cocaine-seeking in an animal model of relapse. The present study investigated the effects of combining wheel running and ATO versus each treatment alone on cocaine-seeking precipitated by cocaine and cocaine-paired cues in rats with differing susceptibility to drug abuse (i.e., high vs. low impulsive). Methods: Rats were screened for high (HiI) or low impulsivity (LoI) based on their performance on a delay-discounting task and then trained to self-administer cocaine (0.4 mg/kg/inf) for 10 days. Following 14 days of extinction, both groups were tested for reinstatement of cocaine-seeking precipitated by cocaine or cocaine-paired cues in the presence of concurrent running wheel access (W), pretreatment with ATO, or both (W+ATO). Results: HiI rats acquired cocaine self-administration more quickly than LoI rats. While both individual treatments and W+ATO significantly attenuated cue-induced cocaine seeking in HiI and LoI rats, only W+ATO was effective in reducing cocaine-induced reinstatement compared with vehicle treatment. There were dose-dependent and phenotype-specific effects of ATO with HiI rats responsive to the low but not high ATO dose. Floor effects of ATO and W on cue-induced reinstatement prevented the assessment of combined treatment effects. Conclusions: These findings demonstrated greater attenuation of cue- versus cocaine-induced reinstatement by ATO and W alone and recapitulate impulsivity phenotype differences in both acquisition of cocaine self-administration and receptivity to treatment.

Original languageEnglish (US)
Pages (from-to)1049-1059
Number of pages11
Issue number6
StatePublished - Mar 2015

Bibliographical note

Funding Information:
The authors would like to thank Vanessa Adamson, Yosef Amrami, Cole Batty, Luke Bushman, Clare Chamberlain, Nathan Holtz, Seth Johnson, Sarah Korthauer, Nathan Omdalen, Amy Saykao, Heather Veglahn, and Ashley Xiong for technical assistance and Krista Walkowiak, DVM, for veterinary care. Funding for this study was provided by the National Institute on Drug Abuse grants T32 DA007097 (PI: Thomas W. Molitor), F31 DA036248 (NEZ), R01 DA003240 (MEC), and K05 DA015267 (MEC).

Publisher Copyright:
© 2014 Springer-Verlag Berlin Heidelberg.


  • Atomoxetine
  • Cocaine
  • Exercise
  • Impulsivity
  • Reinstatement
  • Relapse
  • Wheel running


Dive into the research topics of 'Effects of the combination of wheel running and atomoxetine on cue- and cocaine-primed reinstatement in rats selected for high or low impulsivity'. Together they form a unique fingerprint.

Cite this