Circadian rhythms shift time

A role for the 5-HT7 receptor in the regulation of circadian rhythms has been implicated. As discussed above, 5-HT has been known for some time to induce phase shifts in behavioral circadian rhythms and modulate neuronal activity in the suprachiasmatic nucleus, the likely site of the mammalian circadian clock. The pharmacological characteristics of the effect of 5-HT on circadian rhythms are consistent with 5-HT7 receptor. Moreover, mRNA for the 5-HT7 receptor is found in the suprachiasmatic nucleus. There is also increasing evidence that the 5-HT7 receptor may play a role in psychiatric disorders. The regional distribution of 5-HT7 receptors in brain includes limbic areas and cortex. Atypical antipsychotics, such as clozapine and risperidone, and some antidepressants display high affinity for this receptor. In the periphery, 5-HT7 receptors havebeenshown to mediate relaxation of vascular smooth muscle. 

Furukawa T, Manabe S, Watanabe T et al 1999 Daily fluctuation of hepatic P450 mono-oxygenase activities in male rats is controlled by the suprachiasmatic nucleus but remains unaffected by adrenal hormones. Arch Toxicol 73 367-372 Gillette MU 1986 The suprachiasmatic nuclei. Circadian phase-shifts induced at the time of hypothalamic slice preparation are preserved in vitro. Brain Res 379 176-181 Guo YF, Stein K 2003 Circadian rhythm in the cardiovascular system. Chronocardiology. jAm Heart J 145 779-786... 

Fig. 11.2. Circadian rhythm of bioluminescence in Gonyaulax polyedra (Taylor et al., 1989b). The curves in (a) show phase-shifts of the rhythm by pulses of anisomycin, an inhibitor of protein synthesis. The concentration of anisomycin used is indicated along the vertical axis, as well as the time at which the drug is administered. Experiments shown indicate phase-shifts produced by 1 h pulses of 0.1 pM (vials 2 and 20) and 0.2 pM (vials 3 and 21) anisomycin. Vertical lines indicate positions of control peaks (vials 7 and 25). Drug pulses given between hours 11 and 12 (vials 2 and 3) resulted in phase delays as compared to control (vial 7) pulses given from hours 14 to 15 resulted in phase advances compared to control (vial 25). (b) A phase response curve for 1 h pulses of 0.3 pM anisomycin. Conditions are as in (a). Time on the abscissa denotes beginning of the pulses, in hours since cells were transferred to constant conditions. A positive phase shift denotes a phase advance.

The most important characteristic of the human circadian system for the shiftworker is that much of it is resistant to abrupt changes in schedule. This means that the circadian rhythm will continue to cycle in a way that is not adapted to current working patterns for some time, possibly weeks or even months. Note that circadian rhythms never fully adapt, even in cases where the operator is working on a permanent night shift The practical effect of this is that the operator s circadian rhythm can be caUing for sleep when... 

Evidence for the involvement of ocular photoreception came from the characterization of the norpA mutation in flies, which renders them eyeless and devoid of ocellar function. Flies harbouring this mutation take a longer time to re-entrain their activity rhythms to a shifted LD cycle (Helfrich-Forster et al 2001). However, the observation that they still entrain suggested involvement of a second system in circadian photoperception. 

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