Differential response to a selective cannabinoid receptor antagonist (SR141716: Rimonabant) in female mice from lines selectively bred for high voluntary wheel-running behaviour

Brooke K. Keeney, David A. Raichlen, Thomas H. Meek, Rashmi S. Wijeratne, Kevin M. Middleton, Gregory L. Gerdeman, Theodore Garland

Research output: Contribution to journalArticle

56 Scopus citations


Exercise is a naturally rewarding behaviour in human beings and can be associated with feelings of euphoria and analgesia. The endocannabinoid system may play a role in the perception of neurobiological rewards during and after prolonged exercise. Mice from lines that have been selectively bred for high voluntary wheel running (high runner or HR lines) may have evolved neurobiological mechanisms that increase the Incentive salience of endurance-type exercise. Here, we test the hypothesis that endocannabinoid signalling has been altered In the four replicate HR lines as compared with four nonselected control lines. After 18 days of acclimation to cages with attached wheels, we injected mice with rimonabant (SR141716), a selective cannabinoid CB1 receptor antagonist During the time of normal peak running, each mouse received, in a randomized order, intraperitonial infection of rimonabant (0.1 or 3.0 mg/kg) or vehicle, over 9 days. Drug response was quantified as wheel revolutions, time and speed 10-70 min postinjection. Rimonabant decreased running in all mice; however, female HR mice differentially decreased running speed and distance (but not time) as compared with control females. We conclude that altered endocannabinoid signalling plays a role in the high wheel running of female HR mice.

Original languageEnglish (US)
Pages (from-to)812-820
Number of pages9
JournalBehavioural Pharmacology
Issue number8
StatePublished - Dec 1 2008



  • Artificial selection
  • Endocannabinoids
  • Exercise
  • Experimental evolution
  • Genetics
  • Hyperactivity
  • Locomotor acitivity
  • Mouse
  • Rimonabant
  • Sex differences
  • Wheel running

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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