The suprachiasmatic nucleus of the hypothalamus (SCN) drives daily rhythms of physiology and behavior. Previous studies suggest a role for cannabinoids in regulating circadian rhythms, acting through the cannabinoid type 1 receptor (CB1). To further evaluate endocannabinoids in clock regulation, we screened CB1 knockout mice (CB1-/-) for circadian clock abnormalities. These mice show increased circadian disorganization, with some displaying increased wheel-running activity during the light phase of the light-dark cycle. In both constant dark and in constant light, CB1-/- mice show free-running periods that are significantly shorter than in wild-type controls. CB1-/- mice also show increased phase shifts in response to light pulses compared to control mice. Next, we evaluated the response of the mice to 6 hour phase advance and delays of the light-dark cycle (simulated jet lag). Reentrainment rates appeared to be faster in the CB1-/- mice, however, this was difficult to evaluate due to disruption of the rhythmic activity pattern. We then evaluated food anticipatory activity (FAA) during timed restricted feeding in mice under both a light-dark cycle and in constant light. Because CB1-/- mice show a very lean phenotype, we expected to find reduced FAA. Results suggest that CB1-/- show FAA that is equal to or greater than wild type mice. Finally, we assessed neuronal activation in the SCN in response to light pulses using expression of the gene Fos, but found no significant differences between CB1-/- and wild type mice. These data suggest that cannabinoids alter clock function through actions downstream of light input pathways.
Dr. Ashutosh Rastogi
Dr. Eric Mintz
The suprachiasmatic nucleus of the hypothalamus drives daily rhythms of physiology and behavior. We investigated the role of endocannabinoids in regulating circadian rhythms, using mice lacking the cannabinoid type 1 receptor (CB1). Mice showed a number of behavioral differences from unaltered mice, including circadian disorganization, shorter free-running periods, and increased phase shifts in response to light pulses. After phase advances and delays CB1-/- mice display faster reentrainment rates compared to wild type mice. Mice show normal or increased food anticipatory activity to timed restricted feeding, but no increase in neuronal activation after nocturnal light pulses. These data suggest that cannabinoids play an important role in regulating circadian rhythms.