Interrelationship of CB1R and OBR pathways in regulation of metabolic, neuroendocrine, and behavioral responses to food restriction and voluntary wheel running

Abdoulaye Diane, Donna F. Vine, James C. Russell, C. Donald Heth, W. David Pierce, Spencer D. Proctor

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3 Citations (Scopus)


We hypothesized the cannabinoid- 1 receptor and leptin receptor (ObR) operate synergistically to modulate metabolic, neuroendocrine, and behavioral responses of animals exposed to a survival challenge (food restriction and wheel running). Obese-prone (OP) JCR:LA-cp rats, lacking functional ObR, and lean-prone (LP) JCR:LA-cp rats (intact ObR) were assigned to OP-C and LP-C (control) or CBR1-antagonized (SR141716, 10 mg/kg body wt in food) OP-A and LP-A groups. After 32 days, all rats were exposed to 1.5-h daily meals without the drug and 22.5-h voluntary wheel running, a survival challenge that normally culminates in activity-based anorexia (ABA). Rats were removed from the ABA protocol when body weight reached 75% of entry weight (starvation criterion) or after 14 days (survival criterion). LP-A rats starved faster (6.44 ± 0.24 days) than LP-C animals (8.00 ± 0.29 days); all OP rats survived the ABA challenge. LP-A rats lost weight faster than animals in all other groups (P < 0.001). Consistent with the starvation results, LP-A rats increased the rate of wheel running more rapidly than LP-C rats (P < 0.001), with no difference in hypothalamic and primary neural reward serotonin levels. In contrast, OP-A rats showed suppression of wheel running compared with the OP-C group (days 6-14 of ABA challenge, P < 0.001) and decreased hypothalamic and neural reward serotonin levels (P < 0.01). Thus there is an interrelationship between cannabinoid-1 receptor and ObR pathways in regulation of energy balance and physical activity. Effective clinical measures to prevent and treat a variety of disorders will require understanding of the mechanisms underlying these effects.

Original languageEnglish
Pages (from-to)97-104
Number of pages8
JournalJournal of Applied Physiology
Issue number2
Publication statusPublished - 15 Jul 2014
Externally publishedYes



  • Activity-based anorexia
  • CB1R
  • Food restriction
  • JCR:LA-cp rats
  • ObR
  • SR141716
  • Wheel running

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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