Meeting Abstract
2.4 Monday, Jan. 4 Sex-Specific Involvement of the CB1 Receptor in the High Voluntary Wheel Running of Selectively Bred Mice KEENEY, B.K.*; MEEK, T.H.; MIDDLETON, K.M.; HOLNESS, L.; GERDEMAN, G.L.; RAICHLEN, D.A.; GARLAND, T. Jr.; University of California, Riverside; University of California, Riverside; California State University San Bernardino; University of California, Riverside; Eckerd College; University of Arizona; University of California, Riverside bkeen001@ucr.edu
The endocannabinoid signaling system is complex, influences multiple regulatory systems, and may also play an important role in voluntary exercise. In particular, the cannabinoid receptor CB1 is known to mediate aspects of voluntary motor function, energy balance, appetite, and analgesia. Previously, we found that a CB1 receptor antagonist (rimonabant or SR141716) differentially and sex-specifically inhibits the wheel running of mice from lines selectively bred for high voluntary wheel running (HR lines)(Behavioural Pharmacology, 2008, 19:812-820). In the present study, we investigated the CB1 agonist WIN 55,212-2 (WIN). Mice were acclimated to cages with attached wheels for ~21 days. Near the end of this period, HR mice were running ~2.5-fold more revolutions/day than C mice. Then, during the time of peak nightly wheel running, each mouse received a low (0.5 mg/kg), medium (1 mg/kg), or high (3 mg/kg) dose of WIN, or a vehicle (20% DMSO, 10% Tween-80 and 70% physiological saline) injection, in randomized order over a period of 12 days. Drug response was quantified as wheel revolutions 10-70 and 70-120 minutes post-injection. We also analyzed average speed (revs/min) and time spent running (min). Nested analysis of covariance for repeated measures indicated that WIN decreased wheel running in all mice; however, the dose-by-linetype interaction was statistically significant for males but not females. These results, in combination with those obtained previously for rimonabant, suggest complex and sex-specific associations between wheel-running behavior and the endocannabinoid system. Supported by NSF IOB-0543429 to T.G.
