Autoradiographic localization of 2-[125I]iodomelatonin binding sites in the brains of C3H/HeN and C57BL/6J strains of mice

doi:10.1016/0014-2999(90)90328-4

European Journal of Pharmacology

Volume 180, Issues 2–3, 16 May 1990, Pages 387-390

https://doi.org/10.1016/0014-2999(90)90328-4 Get rights and content

Abstract

The present study uses in vitro autoradiography to localize 2-[¹²⁵I]iodemelatonin binding sites in the brain of two strains of mice, the C3H/HeN and the C57BL/6J, which have been shown to exhibit differences in pineal melatonin content. We found a differential pattern of distribution of 2-[¹²⁵I]iodomelatonin binding sites between the two strains with the suprachiasmatic nucleus, paraventricular nucleus of the thalamus, regions labelled in both strains. These studies should help to interpret behavioral changes due to activation of melatonin receptors in these strains of mice.

References (10)

S. Ebihara et al.
Entrainment of the circadian activity rhythm to the light cycle: Effective light intensity for a zeitgeber in the retinal degenerate C3H mouse and the normal C57BL mouse
Physiol. Behav.
(1980)
G.J.M. Maestroni et al.
Role of the pineal gland in immunity: Circadian synthesis and the release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone
J. Neuroimmunol.
(1986)
M.L. Dubocovich
Pharmacology and function of melatonin receptors
FASEB J.
(1988)
Dubocovich, M.L., E. Mogilnicka and P.M. Areso, Antidepressant like activity of the melatonin receptor antagonist...
S. Ebihara et al.
Genetic control of melatonin synthesis in the pineal gland of the mouse
Science
(1986)

There are more references available in the full text version of this article.

Cited by (66)

The location, physiology, pathology of hippocampus Melatonin MT<inf>2</inf> receptor and MT<inf>2</inf>-selective modulators
2023, European Journal of Medicinal Chemistry
Melatonin, a neurohormone secreted by the pineal gland and regulated by the suprachiasmatic nucleus (SCN) of the hypothalamus, is synthesized and directly released into the cerebrospinal fluid (CSF) of the third ventricle (3rdv), where it undergoes rapid absorption by surrounding tissues to exert its physiological function. The hippocampus, a vital structure in the limbic system adjacent to the ventricles, plays a pivotal role in emotional response and memory formation. Melatonin MT₁ and MT₂ receptors are G protein-coupled receptors (GPCRs) that primarily mediate melatonin's receptor-dependent effects. In comparison to the MT₁ receptor, the widely expressed MT₂ receptor is crucial for mediating melatonin's biological functions within the hippocampus. Specifically, MT₂ receptor is implicated in hippocampal synaptic plasticity and memory processes, as well as neurogenesis and axogenesis. Numerous studies have demonstrated the involvement of MT₂ receptors in the pathophysiology and pharmacology of Alzheimer's disease, depression, and epilepsy. This review focuses on the anatomical localization of MT₂ receptor in the hippocampus, their physiological function in this region, and their signal transduction and pharmacological roles in neurological disorders. Additionally, we conducted a comprehensive review of MT₂ receptor ligands used in psychopharmacology and other MT₂-selective ligands over recent years. Ultimately, we provide an outlook on future research for selective MT₂ receptor drug candidates.
Physiological, behavioral and environmental factors influence bifurcated circadian entrainment in mice
2019, Physiology and Behavior
Citation Excerpt :
C57BL/6 mice may be considered “melatonin-deficient” because they are incapable of producing endogenous melatonin [38,39]. As they retain competent melatonin receptor function [40–42], this mouse strain is an attractive model to study the effects of melatonin supplementation on circadian function. Because bifurcation is proposed to rely on altered coupling of circadian oscillators [5,14,29] and melatonin may alter this coupling [43], we hypothesized that addition of melatonin to the drinking water would alter the dynamics of the emergence of bifurcation in the progressive photoperiod assay.
Under permissive conditions, mice and hamsters exposed to a polyphasic light regime consisting of two light and two dark phases every 24 h (Light:Dark:Light:Dark; LDLD) can adopt a bifurcated entrainment pattern with roughly equal amounts of running wheel activity in each of the two nights. This rhythm “bifurcation” has significant after-effects on increased circadian adaptability: Mice that have been bifurcated show accelerated rates of re-entrainment after a sudden phase shift and have a markedly expanded range of entrainment. Identifying environmental and physiological factors that facilitate or prevent rhythm bifurcation in LDLD conditions will contribute to an understanding of mechanisms underlying enhanced circadian plasticity. Here we investigate the effects of sex, age, light intensity, access to a running wheel, melatonin, and diet composition on bifurcation behaviors of mice (C57Bl/6 J) exposed to LDLD. Female mice and young mice (<20 weeks) express more symmetrically bifurcated activity compared to male mice and older mice (>30 weeks). Additionally and independently, higher photophase intensities (~500 lx) predict more symmetric entrainment than low levels of light (~50 lx). Without access to a functional running-wheel, mice do not adopt bimodal activity patterns and only transiently maintain them, suggesting that high levels of aerobic activity are necessary for rhythm bifurcation. Neither a lifetime exposure to melatonin administered in the drinking water nor a high fat diet affected bifurcation. Collectively, these results demonstrate that circadian plasticity can be strongly modulated by intrinsic and extrinsic factors. With enhanced mechanistic understanding of this modulation, it may be possible to render human clocks more adaptable and thereby ameliorate negative consequences associated with repeated jet-lag or shift-work.
Synchronizing effects of melatonin on diurnal and circadian rhythms
2018, General and Comparative Endocrinology
Citation Excerpt :
Both membrane bound melatonin receptor subtypes, MT1 and MT2, have been detected in the SCN of most mammals. Whereas MT1 and MT2 receptor mRNA and protein have been reported in the SCN of mice and rat (Dubocovich et al., 1998; Hunt et al., 2001; Reppert et al., 1988; Siuciak et al., 1990), the MT2 receptor cannot be detected by receptor autoradiography with 2-iodomelatonin (Poirel et al., 2002), probably due to its low expression. In vitro studies revealed that both receptors serve different functions in the SCN.
In mammals, the rhythmic secretion of melatonin from the pineal gland is driven by the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. The robust nightly peak of melatonin secretion is an output signal of the circadian clock and is supposed to deliver the circadian message to the whole of the organism.
Since the circadian system regulates many behavioral and physiological processes, its disruption by external (shift-work, jet-lag) or internal desynchronization (blindness, aging) causes many different health problems. Externally applied melatonin is used in humans as a chronobiotic drug to treat desynchronization and circadian disorders, and the success of these treatments does, at first glance, underline the supposed pivotal role of melatonin in the synchronization of the circadian system.
On the other hand, pinealectomy in experimental animals and humans does not abolish their rhythms of rest and activity. Furthermore, mice with deficient melatoninergic systems neither display overt defects in their rhythmic behavior nor do they show obvious signs of disease susceptibility, let alone premature mortality. During the last years, our laboratory has investigated several mouse stains with intact or compromised internal melatonin signaling systems in order to better understand the physiological role of the melatoninergic system. These and other investigations which will be reviewed in the present contribution confirm the synchronizing effect of endogenous melatonin and the melatoninergic system. However, these effects are subtle. Thus melatonin does not appear as the master of internal synchronization, but as one component in a cocktail of synchronizing agents.
Seasonal Regulation of Reproduction in Mammals
2015, Knobil and Neill's Physiology of Reproduction: Two-Volume Set
Most mammals use photoperiod to synchronize their breeding season, so that young are raised during the spring and summer months. The pineal hormone melatonin is the major endocrine message used to relay photoperiodic information to the reproductive axis. This chapter first discusses the ecological context for seasonal breeding and the pivotal role that nocturnal melatonin secretion plays in its regulation. Melatonin acts through high affinity G protein–coupled receptors, and we discuss the emergence of the pars tuberalis of the anterior pituitary as a principal site of melatonin action. We go on to discuss recent evidence that local metabolism of thyroid hormone by tanycyte cells within the mediobasal hypothalamus is the key seasonal gateway for activation of the hypothalamic gonadotropin-releasing hormone pulse generator. Melatonin controls tanycyte function via a pathway involving a novel paracrine action of thyrotropin released by pars tuberalis cells. Downstream targets of this control pathway include RF-amide neurons implicated in hypothalamic gonadotropic signaling, suggesting an integrated model for the control of seasonal reproduction in mammals. We end by focusing on current hypotheses for mechanisms of tanycyte action and the cellular consequences of altered hypothalamic triiodothyronine metabolism.
Genetic deletion of MT<inf>1</inf> melatonin receptors alters spontaneous behavioral rhythms in male and female C57BL/6 mice
2014, Hormones and Behavior
Citation Excerpt :
Deletion of MT1 receptors in C57 mice also increased immobility on the forced swim test and impaired pre-pulse inhibition in the acoustic startle/pre-pulse inhibition test (Weil et al., 2006). The heterogeneous distribution of MT1 receptors in the brain (Adamah-Biassi et al., 2014; Siuciak et al., 1990; Weaver et al., 1989) further suggests that this receptor subtype modulates complex behaviors. However, the role of endogenous melatonin and MT1 receptors in the regulation of daily spontaneous behaviors remains largely uncharacterized.
Behaviors vary over the 24 h light/dark cycle and these temporal patterns reflect in part modulation by circadian neural circuits and hormones, such as melatonin. The goal of this study was to investigate the involvement of MT₁ melatonin receptors in behavioral regulation by comparing male and female C57 wild type (WT) mice with C57 mice with genetic deletion of the MT₁ receptor (MT₁KO). A comprehensive array of fifteen distinct spontaneous behaviors was recorded continuously in the homecage over multiple days using the HomeCageScan system. Behaviors assessed were activity-like (i.e. come down, hang, jump, walk), exploration-like (i.e. dig, groom, rear up, sniff, stretch), resting-like (i.e. awake, remain low, rest, twitch) and ingestion-like (i.e. drink, eat). Phenotypic array and temporal distribution analysis revealed distinct behavioral rhythms that differed between WT and MT₁KO mice. The rhythms were consistent from day to day in males and varied with the estrous cycle in females. We also studied the role of MT₁ receptors on depressive and anxiety-like behaviors. Genetic deletion of MT₁ receptors increased immobility time in the forced swim test and decreased the number of marbles buried in the marble burying test in both male and female C57 mice. We conclude that MT₁ melatonin receptors are involved in neural pathways modulating diurnal rhythms of spontaneous behavior in the homecage as well as pathways regulating depressive and anxiolytic-like behaviors.
Automated video analysis system reveals distinct diurnal behaviors in C57BL/6 and C3H/HeN mice
2013, Behavioural Brain Research
Citation Excerpt :
C57 mice are widely used to generate transgenic mice due to its permissive background for maximal expression of most mutations and its ability to live longer with fewer tumors [13]. This strain of mice expresses melatonin receptors in different areas of the brain and the retina [11,14]. C57 mice produce a low level of melatonin in the pineal gland [12,15] due to a natural point mutation in the amino acid sequence of the aralkylamine N-acetyltransferase (AANAT) gene [16].
Advances in rodent behavior dissection using automated video recording and analysis allows detailed phenotyping. This study compared and contrasted 15 diurnal behaviors recorded continuously using an automated behavioral analysis system for a period of 14 days under a 14/10 light/dark cycle in single housed C3H/HeN (C3H) or C57BL/6 (C57) male mice. Diurnal behaviors, recorded with minimal experimental interference and analyzed using phenotypic array and temporal distribution analysis showed bimodal and unimodal profiles in the C57 and C3H mice, respectively. Phenotypic array analysis revealed distinct behavioral rhythms in Activity-Like Behaviors (i.e. walk, hang, jump, come down) (ALB), Exploration-Like Behaviors (i.e. dig, groom, rear up, sniff, stretch) (ELB), Ingestion-Like Behaviors (i.e. drink, eat) (ILB) and Resting-Like Behaviors (i.e. awake, remain low, rest, twitch) (RLB) of C3H and C57 mice. Temporal distribution analysis demonstrated that strain and time of day affects the magnitude and distribution of the spontaneous homecage behaviors. Wheel running activity, water and food measurements correlated with timing of homecage behaviors. Subcutaneous (3 mg/kg, sc) or oral (0.02 mg/ml, oral) melatonin treatments in C57 mice did not modify either the total 24 h magnitude or temporal distribution of homecage behaviors when compared with vehicle treatments. We conclude that C3H and C57 mice show different spontaneous activity and behavioral rhythms specifically during the night period which are not modulated by melatonin.

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Short communicationAutoradiographic localization of 2-[125I]iodomelatonin binding sites in the brains of C3H/HeN and C57BL/6J strains of mice

Abstract

Physiol. Behav.

J. Neuroimmunol.

Pharmacology and function of melatonin receptors

FASEB J.

Genetic control of melatonin synthesis in the pineal gland of the mouse

Science

Short communication
Autoradiographic localization of 2-[¹²⁵I]iodomelatonin binding sites in the brains of C3H/HeN and C57BL/6J strains of mice