Circadian regulation of retinomotor movements. I. Interaction of melatonin and dopamine in the control of cone length

In lower vertebrates, cone retinomotor movements occur in response to changes in lighting conditions and to an endogenous circadian clock. In the light, cone myoids contract, while in the dark, they elongate. In order to test the hypothesis that melatonin and dopamine may be involved in the regulation of cone movement, we have used an in vitro eyecup preparation from Xenopus laevis that sustains light- and dark-adaptive cone retinomotor movement. Melatonin mimics darkness by causing cone elongation. Dark- and melatonin-induced cone elongation are blocked by dopamine. Dopamine also stimulates cone contraction in dark-adapted eyecups. The effect of dopamine appears to be mediated specifically by a dopamine receptor, possibly of the D2 type. The dopamine agonist apomorphine and the putative D2 agonist LY171555 induced cone contraction. In contrast, the putative D1 agonist SKF38393-A and specific alpha 1-, alpha 2-, and beta-adrenergic receptor agonists were without effect. Furthermore, the dopamine antagonist spiroperidol not only blocked light-induced cone contraction, but also stimulated cone elongation in the light. These results suggest that dopamine is part of the light signal for cone contraction, and that its suppression is part of the dark signal for cone elongation. Melatonin may affect cone movement indirectly through its influence on the dopaminergic system.     

Rapid alterations in corticostriatal ensemble coordination during acute dopamine-dependent motor dysfunction

Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex during hyperdopaminergia ( approximately 500% of controls) with hyperkinesia, and after rapid and profound dopamine depletion (<0.2%) with akinesia in the same animal. Surprisingly, although most cortical and striatal neurons ( approximately 70%) changed firing rate during the transition between dopamine-related hyperkinesia and akinesia, the overall cortical firing rate remained unchanged. Conversely, neuronal oscillations and ensemble activity coordination within and between cortex and striatum did change rapidly between these periods. During hyperkinesia, corticostriatal activity became largely asynchronous, while during dopamine-depletion the synchronicity increased. Thus, dopamine-related disorders like Parkinson's disease may not stem from changes in the overall levels of cortical activity, but from dysfunctional activity coordination in corticostriatal circuits.     

Circadian uses of melatonin in humans

Melatonin in humans can be an independent or dependent variable. Measurement of endogenous melatonin levels under dim-light conditions, particularly the dim-light melatonin onset (DLMO), has received increasing attention among researchers, and for clinicians it may soon become a convenient test that can be done at home using saliva collections in the evening, without interfering with sleep. Melatonin, even at low physiological doses, can cause advances (shifts to an earlier time) or delays (shifts to a later time) depending on when it is administered on its phase-response curve (in most sighted people, these times are approximately in the p.m. and in the a.m., respectively). Although both bright light and melatonin can be used separately or together in the treatment of circadian phase disorders in sighted people-such as advanced and delayed sleep phase syndromes, jet lag, shift-work maladaptation, and winter depression (seasonal affective disorder, or SAD)-melatonin is the treatment of choice in totally blind people. These people provide a unique opportunity to study the human circadian system without the overwhelming effects of ocularly mediated light, thus permitting us to establish that all blind free-runners (BFRs) studied under high resolution appear to have phase-advancing and phase-delaying responses to as yet unidentified zeitgebers (time givers) that are usually too weak to result in entrainment.     

Regulation of seasonal reproductive activity in the stallion, ram and hamster

This review considers seasonal reproduction in male animals with emphasis on the stallion, ram and hamster. The pineal hormone melatonin is the common link between photoperiod and reproduction. An increase in the daily diurnal period of melatonin secretion is associated with a decrease in GnRH release in long-day breeders, but an increase in GnRH release in short-day breeders. Melatonin influences GnRH release within or close to the mediobasal hypothalamus in rams; whereas melatonin receptors have not been found in the hypothalamus of horses. Prolactin release is positively correlated with daylength. Prolactin concentrations are consequently low during the breeding season of sheep and high during the breeding season of horses and hamsters. Prolactin stimulates testicular function in rams. Seasonal changes in GnRH release in the horse are regulated by changes in a GnRH-inhibitory opioidergic tone. Opioids are at least, in part, responsible for the decrease in testicular function during winter. An opioidergic inhibition of LH release is present during the breeding season in rams; but dopaminergic pathways inhibit LH release during long daylight hours. A dopaminergic inhibition of LH release does not exist in stallions.     

Melatonin: Nature's most versatile biological signal?

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin's cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immune-enhancing and oncostatic properties. Its 'chronobiotic' properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder. Melatonin acting as an 'internal sleep facilitator' promotes sleep, and melatonin's sleep-facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin's role as a 'photoperiodic molecule' in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body's physiological functions.     

Circadian Uses of Melatonin in Humans

Melatonin in humans can be an independent or dependent variable. Measurement of endogenous melatonin levels under dim‐light conditions, particularly the dim‐light melatonin onset (DLMO), has received increasing attention among researchers, and for clinicians it may soon become a convenient test that can be done at home using saliva collections in the evening, without interfering with sleep. Melatonin, even at low physiological doses, can cause advances (shifts to an earlier time) or delays (shifts to a later time) depending on when it is administered on its phase‐response curve (in most sighted people, these times are approximately in the p.m. and in the a.m., respectively). Although both bright light and melatonin can be used separately or together in the treatment of circadian phase disorders in sighted people—such as advanced and delayed sleep phase syndromes, jet lag, shift‐work maladaptation, and winter depression (seasonal affective disorder, or SAD)—melatonin is the treatment of choice in totally blind people. These people provide a unique opportunity to study the human circadian system without the overwhelming effects of ocularly mediated light, thus permitting us to establish that all blind free‐runners (BFRs) studied under high resolution appear to have phase‐advancing and phase‐delaying responses to as yet unidentified zeitgebers (time givers) that are usually too weak to result in entrainment.     

Melatonin and the seasonal control of reproduction.

Many mammalian species from temperate latitudes exhibit seasonal variations in breeding activity which are controlled by the annual photoperiodic cycle. Photoperiodic information is conveyed through several neural relays from the retina to the pineal gland where the light signal is translated into a daily cycle of melatonin secretion: high at night, low in the day. The length of the nocturnal secretion of melatonin reflects the duration of the night and it regulates the pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Changes in GnRH release induce corresponding changes in luteinising hormone secretion which are responsible for the alternating presence or absence of ovulation in the female, and varying sperm production in the male. It is not yet known where and how this pineal indoleamine acts to exert this effect. Although melatonin binding sites are preferentially localised in the pars tuberalis (PT) of the adenohypophysis, the hypothalamus contains the physiological target sites of melatonin for its action on reproduction. Melatonin does not seem to act directly on GnRH neurons; rather it appears to involve a complex neural circuit of interneurons that includes at least dopaminergic, serotoninergic and excitatory aminoacidergic neurons.     

Melatonin suppresses iron-induced neurodegeneration in rat brain

The antioxidative action of melatonin on iron-induced neurodegeneration in the nigrostriatal dopaminergic system was evaluated in vivo. Intranigral infusion of iron chronically degenerated the dopaminergic transmission of the nigrostriatal system. An increase in lipid peroxidation in the infused substantia nigra and reductions in dopamine levels and dopaminergic terminals in the ipsilateral striatum were observed 7 d after iron infusion. Whereas local infusion of melatonin (60 microg/microl, 1 microl) alone did not alter dopaminergic transmission, coinfusion of melatonin with iron suppressed iron-induced oxidative damages. Systemic infusion of melatonin via osmotic pumps had no effect on iron-induced neurodegeneration. However, repetitive intraperitoneal injections of melatonin (10 mg/kg) prevented iron-induced oxidative injuries. The ratio of glutathione (GSH)/oxidized glutathione (GSSG) was moderately increased in the lesioned substantia nigra of the melatonin-treated rats compared to that of the lesioned group in control rats. The antioxidative effect of melatonin was verified in cortical homogenates. Melatonin dose-dependently suppressed autoxidation and iron-induced lipid peroxidation. Melatonin was as effective as GSH and was less effective than Trolox (a water-soluble analogue of vitamin E) in inhibiting iron-elevated lipid peroxidation of brain homogenates. Our data suggest that melatonin is capable of at least partially preventing the iron-induced neurodegeneration in the nigrostriatal dopaminergic system.     

Duration of the melatonin pulse in the hypothalamus controls testicular function in pinealectomized mice (Peromyscus leucopus)

Forty-four pinealectomized white-footed mice (Peromyscus leucopus) were stereotaxically implanted with a guide tube-cannula assembly in the area of the preoptic/anterior hypothalamus. Easy insertion and removal of the melatonin-loaded cannula in the basal medial hypothalamus made it possible to examine whether duration of the melatonin pulse at the putative target site controls reproduction in mice. Mice receiving melatonin every day for 10 h during either the day or night underwent gonadal regression within 7 wk, as indexed by substantial decreases in combined testicular weight and seminal vesicle weight. Sperm production in these mice was also reduced or absent. Melatonin pulses given for 5 h, or as two 5-h pulses (separated by 3 h) did not alter reproduction in that these mice resembled sham-implanted controls. These results indicate that duration of the melatonin pulse, acting in the hypothalamus, may regulate seasonal reproduction in P. leucopus.     

Melatonin the "light of night" in human biology and adolescent idiopathic scoliosis

Melatonin "the light of night" is secreted from the pineal gland principally at night. The hormone is involved in sleep regulation, as well as in a number of other cyclical bodily activities and circadian rhythm in humans. Melatonin is exclusively involved in signalling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. The last decades melatonin has been used as a therapeutic chemical in a large spectrum of diseases, mainly in sleep disturbances and tumours and may play a role in the biologic regulation of mood, affective disorders, cardiovascular system, reproduction and aging. There are few papers regarding melatonin and its role in adolescent idiopathic scoliosis (AIS). Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis) but at present, the data available cannot clearly support this hypothesis. Uncertainties and doubts still surround the role of melatonin in human physiology and pathophysiology and future research is needed.     

KiSS‐1: A Likely Candidate for the Photoperiodic Control of Reproduction in Seasonal Breeders

In seasonal species, photoperiod exerts tight regulation of reproduction to ensure that birth occurs at the most favorable time of yr. A distinct photoneuroendocrine circuit composed of the retina, suprachiasmatic nucleus (SCN) of the hypothalamus, and pineal gland transduces daylength into a rhythmic secretion of melatonin. The duration of the night‐time rise of this hormone conveys daylength information to the organism. Melatonin is known to mediate the control of seasonal reproduction, but how it modulates sexual activity is far from understood. Recent data indicate that the product of the KiSS‐1 gene is a potent stimulator of the hypothalamic‐pituitary‐gonadal axis and may play, together with its receptor GPR54, a central role in the neuroendocrine regulation of gonadotropin secretion. This article briefly reviews these findings and presents arguments that KiSS‐1 could take part in the seasonal control of reproduction.     

Melatonin in the circadian system

In Mammals, the master circadian clock is located in the suprachiasmatic nuclei of the hypothalamus. This clock is synchronized with the astronomical time, essentially by the light/dark cycle. The different zeitgebers studied act on the Per1 and/or Per2 genes from the main molecular loop which initiates the circadian oscillations. Once synchronized with the environment, circadian oscillations are distributed through the organism by efferent signals, and the complex interaction of neural, hormonal and behavioural outputs from the circadian clock drive circadian expression of events, either directly or through coordination of the timing of peripheral oscillators. Melatonin, one of the endocrine output signals of the clock, provides the organism with circadian information, and can be considered as an endogenous synchronizer. Melatonin receptors are present in the suprachiasmatic nuclei which allows the hormone to feed back on the clock. To day, the physiological role of this peculiar feed-back has not yet been established. However, the presence of these receptors indicates that through an action on the circadian clock, exogenous melatonin can affect all levels of the circadian network and its capacity to entrain circadian rhythms to 24 h has been demonstrated. Melatonin is thus a zeitgeber. However, surprisingly, and different from the action mechanism of other zeitgebers on the clock, the chronobiotic effect of melatonin does not implicate Per1 and/or Per2. Rather, Rev-erb alpha could be the link between the physiological action of melatonin and the core of the molecular circadian clock.     

KiSS-1: a likely candidate for the photoperiodic control of reproduction in seasonal breeders

In seasonal species, photoperiod exerts tight regulation of reproduction to ensure that birth occurs at the most favorable time of yr. A distinct photoneuroendocrine circuit composed of the retina, suprachiasmatic nucleus (SCN) of the hypothalamus, and pineal gland transduces daylength into a rhythmic secretion of melatonin. The duration of the night-time rise of this hormone conveys daylength information to the organism. Melatonin is known to mediate the control of seasonal reproduction, but how it modulates sexual activity is far from understood. Recent data indicate that the product of the KiSS-1 gene is a potent stimulator of the hypothalamic-pituitary-gonadal axis and may play, together with its receptor GPR54, a central role in the neuroendocrine regulation of gonadotropin secretion. This article briefly reviews these findings and presents arguments that KiSS-1 could take part in the seasonal control of reproduction.     

Circadian disorganization in experimental arthritis

This review discusses the experimental evidence indicating that arthritis disrupts circadian organization, which was mainly derived from animal studies employing Freund's complete mycobacterial adjuvant (FCA). The defense response to antigenic challenge, mediated in part by cytokines, includes changes in chronobiological central nervous system function, like depressed daily activity, superficial sleep or anorexia. Interferon (IFN)-gamma receptors are detectable in the central circadian pacemaker, the hypothalamic suprachiasmatic nuclei, at a time when the capacity for photic entrainment of the pacemaker became established. The disruptive effects of the systemic injection of IFN on the circadian rhythms of locomotor activity, body temperature and clock-gene mRNA expression have been documented. In the last few years we have examined a number of immune and neuroendocrine circadian rhythms in FCA-injected rats, both in the preclinical phase of arthritis (2-3 days after FCA injection) as well as in the acute phase of the disease (18 days after FCA injection). In arthritic rats, the 24-hour organization of immune and neuroendocrine responses becomes altered. A hormonal pathway involving the circadian secretion of melatonin and a purely neural pathway including, as a motor leg, the autonomic nervous system innervating the lymph nodes were identified. The significant effects of the immune-mediated inflammatory response on the diurnal rhythmicity of adenohypophysial and hypophysiotropic hormones occurred in arthritic rats. Melatonin treatment prevented the alteration in 24-hour rhythms of serum ACTH, prolactin and luteinizing hormone in rats injected with FCA. In addition, melatonin pretreatment prevented the alteration in the 24-hour variation in hypothalamic serotonin and dopamine turnover during the preclinical phase of Freund's adjuvant arthritis in rats. Some pinealectomy-induced immune changes in arthritic rats were also prevented by physiological concentrations of melatonin. Melatonin may play the role of an 'internal synchronizer' for the immune system.     

Melatonin facilitates synchronization of sparrow circadian rhythms to light

We recorded circadian locomotor activity rhythms of house sparrows (Passer domesticus) exposed to low-amplitude light-dark cycles (2∶1 lux) with periods of 22.5 or 24.5 h. Under these conditions the circadian rhythms of the majority of the birds were not synchronized by the light cycle but either free-ran or showed relative coordination. However, when melatonin was administered continuously via subcutaneous silastic implants the rhythms became synchronized. It is proposed that melatonin facilitates synchronization either by weakening the circadian oscillatory system thereby increasing its range of entrainment, or by enhancing circadian sensitivity to the light Zeitgeber. In general, the results suggest that melatonin, besides its well-known phasic effects on the circadian system also has important tonic effects modifying the ease with which circadian systems can be entrained.     

The role of melatonin in the treatment of type 2 diabetes mellitus and Alzheimer's disease

In type 2 diabetes mellitus (T2DM) and its related disorders like obesity, the abnormal protein processing, oxidative stress and proinflammatory cytokines will drive the activation of inflammatory pathways, leading to low-grade chronic inflammation and insulin resistance (IR) in the periphery and impaired neuronal insulin signaling in the brain. Studies have shown that such inflammation and impaired insulin signaling contribute to the development of Alzheimer''s disease (AD). Therefore, new therapeutic strategies are needed for the treatment of T2DM and T2DM-linked AD. Melatonin is primarily known for its circadian role which conveys message of darkness and induces night-state physiological functions. Besides rhythm-related effects, melatonin has anti-inflammatory and antioxidant properties. Melatonin levels are downregulated in metabolic disorders with IR, and activation of melatonin signaling delays disease progression. The aim of this Review is to highlight the therapeutic potentials of melatonin in preventing the acceleration of AD in T2DM individuals through its therapeutic mechanisms, including antioxidative effects, anti-inflammatory effects, restoring mitochondrial function and insulin sensitivity.     

Effects of haloperidol and melatonin on the in situ activity of nigrostriatal tyrosine hydroxylase in male Syrian hamsters

Haloperidol, an antipsychotic drug, was tested for its effects on the in situ activity of nigrostriatal and hypothalamic tyrosine hydroxylase, in control male Syrian hamsters and in those receiving a high daily dose of melatonin. After receiving daily ip injections (1.25 mg/kg ip) of haloperidol for 21 days, the animals were sacrificed and brain tissue collected for analysis of dopamine and metabolites by HPLC with electrochemical detection. In situ activity of tyrosine hydroyxlase (TH) activity was determined by measuring the accumulation of L-Dopa after administration of the L amino acid decarboxylase inhibitor, mhydroxybenzylhydrazine. Tissue content of dopamine and its metabolites, DOPAC and HVA, was depressed in striatum of animals receiving haloperidol, and tyrosine hydroxylase (TH) activity was significantly decreased 20-24 h after the last injection (from 1823 +/- 63 to 1139 +/- 85 pg l-dopa/mg tissue). The decrease in TH activity in striatum was significantly inhibited by daily injections of a high dose of melatonin (2.5 mg/kg ip) (from 1139 +/- 85 to 1560 +/- 116 pg L-dopa/mg tissue). In the substantia nigra and in the hypothalamus, on the other hand, haloperidol significantly increased the activity of tyrosine hydroxylase. Melatonin administration did not significantly influence TH activity in the substantia nigra, but inhibited TH activity in the hypothalamus and in the pontine brainstem. One explanation for these data is that chronic haloperidol administration in Syrian hamsters increases TH activity in hypothalamus and substantia nigra, but decreases TH activity in striatum by a mechanism involving D2 presynaptic receptors and a melatonin sensitive kinase which regulates TH phosphorylation.     

Melatonin relieves diabetic complications and regenerates pancreatic beta cells by the reduction in NF-kB expression in streptozotocin induced diabetic rats

Melatonin, a pleiotropic hormone, has many regulatory effects on the circadian and seasonal rhythms, sleep and body immune system. It is used in the treatment of blind circadian rhythm sleep disorders, delayed sleep phase and insomnia. It is a potent antioxidant, anti-inflammatory, free radical scavenger, helpful in fighting infectious disease and cancer treatment. Decreased level of circulating melatonin was associated with an increased blood glucose level, losing the anti-oxidant protection and anti-inflammatory responses. We aimed to evaluate the effect of melatonin administration, in streptozotocin (STZ) induced diabetic rats, on blood glucose level and pancreatic beta (β) cells. Diabetes mellitus was induced in Sprague dawley male rats by the intravenous (i.v) injection of 65 mg/kg of STZ. Diabetic rats received melatonin at a dose of 10 mg/kg daily for 8 weeks by oral routes. The results showed, after 8 weeks of melatonin administration, a reduction in: 1- fasting blood glucose (FBG) and fructosamine (FTA) levels, 2- kidney and liver function parameters, 3- levels of serum triglycerides, cholesterol and LDL-C, 4- malondialdehyde (MDA), 5- NF-κB expression in treated group, 6- pro-inflammatory cytokines (IL-1β and IL-12) and immunoglobulins (IgA, IgE and IgG). Furthermore, an elevation in insulin secretion was noticed in melatonin treated group that indicated β cells regeneration. Therefore, melatonin administration, in STZ induced diabetic rats; reduced hyperglycemia, hyperlipidemia and oxidative stress. Melatonin acted as an anti-inflammatory agent that reduced pro-inflammatory cytokines (IL-1β and IL-12) and oxidative stress biomarkers (MDA). Melatonin succeeded in protecting β cells under severe inflammatory situations, which was apparent by the regeneration of islets of Langerhans in treated diabetic rats. Moreover, these results can open a gate for diabetes management and treatment.     

Mammalian photoperiodic system: formal properties and neuroendocrine mechanisms of photoperiodic time measurement

Photoperiodism is a process whereby organisms are able to use both absolute measures of day length and the direction of day length change as a basis for regulating seasonal changes in physiology and behavior. The use of day length cues allows organisms to essentially track time-of-year and to "anticipate" relatively predictable annual variations in important environmental parameters. Thus, adaptive types of seasonal biological changes can be molded through evolution to fit annual environmental cycles. Studies of the formal properties of photoperiodic mechanisms have revealed that most organisms use circadian oscillators to measure day length. Two types of paradigms, designated as the external and internal coincidence models, have been proposed to account for photoperiodic time measurement by a circadian mechanism. Both models postulate that the timing of light exposure, rather than the total amount of light, is critical to the organism's perception of day length. In mammals, a circadian oscillator(s) in the suprachiasmatic nucleus of the hypothalamus receives photic stimuli via the retinohypothalamic tract. The circadian system regulates the rhythmic secretion of the pineal hormone, melatonin. Melatonin is secreted at night, and the duration of secretion varies in inverse relation to day length; thus, photoperiod information is "encoded" in the melatonin signal. The melatonin signal is presumably "decoded" in melatonin target tissues that are involved in the regulation of a variety of seasonal responses. Variations in photoperiodic response are seen not only between species but also between breeding populations within a species and between individuals within single breeding populations. Sometimes these variations appear to be the result of differences in responsiveness to melatonin; in other cases, variations in photoperiod responsiveness may depend on differences in patterns of melatonin secretion related to circadian variation. Sites of action for melatonin in mammals are not yet well characterized, but potential targets of particular interest include the pars tuberalis of the pituitary gland and the suprachiasmatic nuclei. Both these sites exhibit uptake of radiolabeled melatonin in various species, and there is some evidence for direct action of melatonin at these sites. However, it appears that there are species differences with respect to the importance and specific functions of various melatonin target sites.     

Changes in light and dark periods affect the arylalkylamine N-acetyl transferase,melatonin activities and redox status in the head and hemolymph of nocturnal insect Spodoptera litura

The present study was conducted to describe the impact of circadian rhythm on melatonin levels and redox statusunder three photoperiods (12L:12D, 0L:24D, and 24L:0D) in head and hemolymph of Spodoptera litura. Melatonin is an powerful antioxidant and controls the reproduction of organisms. In this study, melatonin levels, Arylalkylamine N-acetyltransferase(AA-NAT), and antioxidant enzyme activities were analyzed. Results showed melatonin, AA-NAT levels in hemolymph were significantly (p < 0.05) higher during the dark period than during LL regime. HPLC chromatogram of the insect head and hemolymph showed 5 peaks while hemolymph showed 6 peaks in LD, and LLregimes. The day–night changes of melatonin increased the antioxidant enzymes (GST, CAT, POX) persisted in the insect hemolymph, but were suppressed by constant light. The present study leads us to speculate that synthesis and release of melatonin in the S.litura head occur as circadian rhythm and light has an inhibitory effect on melatonin synthesis.