Mistlberger RE, Antle MC, Jones M, Kilduff TS (2001) Light- and food-entrained circadian rhythms in rats with neurotoxic lesions of hypocretin cells. Neuroscience 2001 Abstracts 410.8. Society for Neuroscience, San Diego, CA.
Summary: The hypocretins (Hcrt1 & 2) are lateral hypothalamic (LH) neuropeptides implicated in the regulation of feeding and sleep-wake states. Hcrt lesions attenuate the amplitude of sleep-wake circadian rhythms in rats entrained to light-dark (LD; Gerashchenko et al, Soc. Neurosci Abst., 2000). We examined whether Hcrt cells also participate in the expression of circadian rhythms entrained by daily feeding schedules. Rats received LH injections of Hcrt2 conjugated to the ribosome- inactivating protein saporin. Drinking was recorded in LD 12:12 for 1-2 months, in DD for 48 h, and in LD 2:2 for 24 h, to assess photic entrainment and masking. The rats were then restricted to a 3 h daily meal beginning 6 h after lights-on (LD 12:12). After 29 days, the rats were deprived of food for 50 h. Lesions, assessed by immunocytochemistry using preprohypocretin antibody (Chemicon Int., Inc.), ranged from 0-100% complete. Complete lesions were associated with attenuated mean level and amplitude of circadian drinking rhythms in LD 12:12 and DD, but photic masking in LD 2:2 was unaffected. All rats exhibited food-entrained activity that anticipated feeding time by 1-3 h. This was of lower magnitude in the rat with the largest lesion. These results are consistent with a recent report that Hcrt2-saporin lesions attenuate sleep-wake circadian rhythms, but differ from earlier reports that electrolytic lesions of the LH may potentiate the masking effects of light on behavior. The results suggest that Hcrt cells do not play an essential role in the regulation of circadian rhythms by scheduled feeding.
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