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J Appl Physiol (1985). 2014 Jul 15;117(2):97-104. doi: 10.1152/japplphysiol.01303.2013. Epub 2014 Jun 5.

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

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Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, Alberta Diabetes Institute, University of Alberta, Alberta, Edmonton, Canada;
Department of Psychology, University of Alberta, Alberta, Edmonton, Canada.
Department of Sociology, University of Alberta, Alberta, Edmonton, Canada; and


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.


CB1R; JCR:LA-cp rats; ObR; SR141716; activity-based anorexia; food restriction; wheel running

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