title: Effect of stimulation of endogenous melatonin secretion during constant light exposure on 6-sulphatoxymelatonin rhythmicity in rats.
abstract: When light is presented unexpectedly at night to rats, melatonin production and secretion is acutely inhibited and the time of onset of production on the subsequent night is altered. In a series of experiments, we examined the effects of 6-12 hr light (200 lux) at night on melatonin metabolite excretion (6-sulphatoxymelatonin, aMT.6S). During the light exposure, we administered isoproterenol to stimulate endogenous production of melatonin by the pineal gland to determine if replacement of melatonin would block any phase shifting effects of the light. Exposure to 6 hr of light either during the first or second half of the night suppressed aMT.6S excretion during the light treatment and delayed the onset of melatonin secretion by 3.7 +/- 0.6 and 2.5 +/- 0.6 hr, respectively, compared to a change of 0.5 +/- 0.1 hr in animals maintained in darkness. Twelve hours light exposure (i.e. one night of continuous light) suppressed aMT.6S excretion completely and resulted in a delay in the onset the next night of 2.1 +/- 0.7 hr. When propranolol (10 mg/kg) was administered at 2-hr intervals during darkness, aMT.6S excretion was suppressed throughout the night, but on the subsequent release into constant darkness the onset of excretion was not delayed (0.6 +/- 0.1 hr delay). Administration of isoproterenol (10 mg/kg) to animals in constant light, at the time of expected lights off (CT12), and 5 hr later (CT17) resulted in an increase in melatonin production and aMT.6S excretion that was similar in duration and amount to the control night. The stimulation of endogenous melatonin production failed to block the phase shifting effects of the light exposure and, in fact, appeared to potentiate the delay at least on the first night (4.2 +/- 0.9 hr). The timing of the release into constant darkness following the light treatment had an unexpected effect on melatonin production on the cycle after treatment. Thus, animals exposed to 12 hr light and released into darkness at the normal time of lights off as above had a delay of about 2 hr and excreted 71 +/- 18% of the aMT.6S excreted on a control night. Animals released into darkness at the expected time of lights on failed to excrete more than 20 pmol/hr(i.e. no onset of excretion could be determined) at any time on the first subjective night after light treatment, which was no different from the excretion during the light treatment. On the next subjective night, the onset was delayed as expected and the amount of aMT.6S produced was restored. Treatment with isoproterenol at CT12 and CT17 failed to affect either the amount of aMT.6S excreted on the first subjective night after light treatment or the phase delay on the second night after treatment. The failure to produce melatonin on the first subjective night after 12 hr light exposure and release into darkness at CTO was not due to failure at the level of the pineal gland since injection ofisoproterenol at CT12 and CT17 on the first subjective night after light restored the normal amount of melatonin production. These results suggest that the absence of melatonin during light stimulation at night is not responsible for the phase delay in melatonin production and excretion on subsequent nights. The basis of the failure of the rats to commence melatonin production following 12 hr extended light exposure followed immediately by continuous darkness is not known.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Adelaide, Medical School, Adelaide, South Australia, Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kennaway
authors.forename: S A
authors.initials: SA
authors.lastname: Rowe
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002940:Circadian Rhythm; D003623:Dark Adaptation; D007545:Isoproterenol / Q000494:pharmacology; D008027:Light; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000652:urine; D017440:Photoperiod; D010870:Pineal Gland / Q000187:drug effects / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; C054513:6-sulfatoxymelatonin; D011433:Propranolol; D008550:Melatonin; D007545:Isoproterenol