Further Evidence of the Melatonin Calmodulin Interaction: Effect on CaMKII Activity.

Melatonin (MEL) is a pleiotropic indolamine that reaches multiple intracellular targets. Among these, MEL binds to calmodulin (CaM) with high affinity. In presence of Ca2+, CaM binds to CaM-dependent kinase II (CaMKII). The Ca2+-CaM/CaMKII pathway regulates a myriad of brain functions in different cellular compartments. Evidence showing the regulation of this cellular pathway by MEL is scarce. Thus, our main objective was to study the interaction of MEL with CaM and its effects on CaMKII activity in two microenvironments (aqueous and lipidic) naturally occurring within the cell. In addition, colocalization of MEL with CaM in vivo was explored in mice brain hippocampus. In vitro CaM-MEL interaction and the structural conformations of CaM in the presence of this indoleamine were assessed through electrophoretic mobility and isoelectric point. The functional consequence of this interaction was evaluated by measuring CaMKII activity. Ca2+-CaM-MEL increased the activity of CaMKII in aqueous buffer but reduced the kinase activity in lipid buffer. Importantly, MEL colocalizes in vivo with Ca2+-CaM in the hippocampus. Our evidence suggests that MEL regulates the key cellular Ca2+-CaM/CaMKII pathway and might explain why physiological MEL concentrations reduce CaMKII activity in some experimental conditions, while in others it drives biological processes through activation of this kinase.

Chronic sleep loss disrupts blood-testis and blood-epididymis barriers, and reduces male fertility.

Sleep loss increases blood-brain barrier permeability. As the blood-brain barrier and the blood-tissue barriers in the reproductive tract (blood-testis and blood-epididymis barriers) share common characteristics, we hypothesized that sleep restriction may also modify their barrier function. Previous reports showed that sleep loss decreased sperm viability and progressive fast mobility, which may be a consequence of altered blood-testis and blood-epididymis barrier. Therefore, we quantified changes in blood-testis and blood-epididymis barrier after sleep loss and related them to male fertility. Adult male Wistar rats were sleep restricted using the multiple-platform technique in a protocol of 20 hr daily sleep deprivation plus 4 hr of sleep recovery in the home-cage. At the 10th day, barrier permeability assays were performed with Na-fluorescein, 10 kDa Cascade blue-dextrans and Evans blue, and the expression of tight junction proteins, actin and androgen receptor was quantified. At the 10th day of sleep restriction and after sleep recovery days 1-7, males were placed with sexually receptive females, sexual behaviour was tested, and the percentage of pregnancies was calculated. Sleep restriction increased the barrier permeability to low- and high-molecular-weight tracers, and decreased the expression of tight junction proteins, actin and androgen receptor. Concomitantly, sleep restriction reduced the percentage of ejaculating males and the number of pregnancies. Sleep recovery for 2-3 days progressively re-established fertility, as indicated by a higher percentage of ejaculating males and impregnated females. In conclusion, chronic sleep loss alters fertility concomitantly with the disruption of the blood-tissue barriers at the reproductive tract, the mechanism involves androgen signalling.

Reduced systemic levels of IL-10 are associated with the severity of obstructive sleep apnea and insulin resistance in morbidly obese humans.

Obstructive sleep apnea (OSA) has been related to elevation of inflammatory cytokines and development of insulin resistance in morbidly obese (MO) subjects. However, it is still unclear whether the systemic concentration of anti-inflammatory mediators is also affected in MO subjects directly related to the severity of OSA and level of insulin resistance. Normal weight and MO subjects were subjected to overnight polysomnography in order to establish the severity of OSA, according to the apnea-hypopnea index (AHI). Blood samples were obtained for estimation of total cholesterol and triglycerides, insulin, glucose, insulin resistance, tumor necrosis factor alpha (TNF-α), interleukin 12 (IL12), and interleukin 10 (IL-10). Serum levels of IL-10 were significantly lower in MO subjects with OSA than in MO and control individuals without OSA. Besides being inversely associated with serum TNF-α and IL-12, decreased IL-10 levels were significantly related to increased AHI, hyperinsulinemia, and insulin resistance. Serum IL-10 is significantly reduced in morbidly obese subjects with severe OSA while also showing a clear relationship with a state of hyperinsulinemia and insulin resistance probably regardless of obesity in the present sample. It may be of potential clinical interest to identify the stimulatory mechanisms of IL-10 in obese individuals with OSA.

Sleep in the spider monkey (Ateles geoffroyi): A semi-restrictive, non-invasive, polysomnographic study.

The normal sleep patterns of the spider monkey (Ateles geoffroyi) have not been described yet. The objective of this study was to characterize the electrophysiological patterns, sleeping postures, and sleep-wake cycle in semi-restricted spider monkeys. Continuous 24-hr polysomnographic (PSG) recordings, involving simultaneous recording of non-invasive electroencephalographic (EEG), electro-oculographic (EOG), and electromyographic (EMG) activities, were carried out in captive monkeys living in outdoor rainforest enclosures. Electrode placement was done according to the human international 10-20 system. Specific behaviors displayed by monkeys during the sleep-wake cycles were correlated with the PSG recordings. The nycthemeral distribution of the sleep-wake cycle was also calculated. The results show that electrophysiological N-REM sleep patterns in spider monkeys are similar to those observed in other primates, including human beings. Furthermore, a vertical semi-fetal posture was observed during N-REM and REM sleep phases. The amount of nocturnal sleep was significantly higher than that of the diurnal period, showing that the spider monkey is a diurnal primate. An outstanding finding was the absence of muscular atonia during the spider monkey's REM sleep, which suggests that arboreal primates have developed a neuromuscular mechanism specialized for sleeping in a vertical posture.

Further definition on the multiple partner choice arena: a potential animal model for the study of premature ejaculation.

INTRODUCTION: The multiple partner choice arena (MPCA) is an experimental setup in which male rats display a significant shortening of ejaculation latency, which is the main characteristic of premature ejaculation (PE) in men. Thus, the MPCA is a potential animal model for PE. AIM: In this study, we further analyze whether the features of the MPCA satisfy the validity criteria for it to be considered an animal model as well as the possible participation of the serotoninergic system in the faster ejaculation exhibited by male rats in the MPCA. METHODS: In Experiment 1, male rats were tested in a standard arena to assess their sexual behavior, then were assessed 1 week later in the MPCA. Another group was first tested in the MPCA, then in a standard arena. In Experiment 2, male rats divided into two groups were treated daily with WAY-100635 (5-HT(1A) antagonist) or vehicle for 15 days. In each group, half of the subjects were tested in a standard arena and half were tested in the MPCA on days 1, 8, and 15 of treatment. MAIN OUTCOME MEASURES: Number of intromissions and intromission and ejaculation latencies were the main outcome measures. RESULTS: In Experiment 1, males tested in the MPCA ejaculated significantly faster, regardless of the order in which they were evaluated in both arenas. In Experiment 2, the administration of WAY-100635 increased intromission and ejaculation latencies, and the number of intromissions in the MPCA. CONCLUSIONS: The results obtained in the MPCA support its use as an animal model for PE evaluation.

Sleep loss as a factor to induce cellular and molecular inflammatory variations.

A reduction in the amount of time spent sleeping occurs chronically in modern society. Clinical and experimental studies in humans and animal models have shown that immune function is impaired when sleep loss is experienced. Sleep loss exerts a strong regulatory influence on peripheral levels of inflammatory mediators of the immune response. An increasing number of research projects support the existence of reciprocal regulation between sleep and low-intensity inflammatory response. Recent studies show that sleep deficient humans and rodents exhibit a proinflammatory component; therefore, sleep loss is considered as a risk factor for developing cardiovascular, metabolic, and neurodegenerative diseases (e.g., diabetes, Alzheimer's disease, and multiple sclerosis). Circulating levels of proinflammatory mediators depend on the intensity and duration of the method employed to induce sleep loss. Recognizing the fact that the concentration of proinflammatory mediators is different between acute and chronic sleep-loss may expand the understanding of the relationship between sleep and the immune response. The aim of this review is to integrate data from recent published reports (2002-2013) on the effects of sleep loss on the immune response. This review may allow readers to have an integrated view of the mechanisms involved in central and peripheral deficits induced by sleep loss.

Differential impact of REM sleep deprivation on cytoskeletal proteins of brain regions involved in sleep regulation.

Rapid eye movement (REM) sleep is involved in memory consolidation, which implies synaptic plasticity. This process requires protein synthesis and the reorganization of the neural cytoskeleton. REM sleep deprivation (REMSD) has an impact on some neuronal proteins involved in synaptic plasticity, such as glutamate receptors and postsynaptic density protein 95, but its effects on cytoskeletal proteins is unknown. In this study, the effects of REMSD on the content of the cytoskeletal proteins MAP2 and TAU were analyzed. Adult female rats were submitted to selective REMSD by using the multiple platform technique. After 24, 48 or 72 h of REMSD, rats were decapitated and the following brain areas were dissected: pons, preoptic area, hippocampus and frontal cortex. Protein extraction and Western blot were performed. Results showed an increase in TAU content in the pons, preoptic area and hippocampus after 24 h of REMSD, while in the frontal cortex a significant increase in TAU content was observed after 72 h of REMSD. A TAU content decrease was observed in the hippocampus after 48 h of REMSD. Interestingly, a marked increase in TAU content was observed after 72 h of REMSD. MAP2 content only increased in the preoptic area at 24 h, and in the frontal cortex after 24 and 72 h of REMSD, without significant changes in the pons and hippocampus. These results support the idea that REM sleep plays an important role in the organization of neural cytoskeleton, and that this effect is tissue-specific.

Changes in pharyngeal anatomy and apnea/hypopnea index after a mandibular advancement device.

Objectives: This study aimed to evaluate the therapeutic effcacy of custom-made mandibular advancement devices (MAD) in the control of primary snoring and sleep apnea and to correlate with anatomical changes identified through imaging tests. Methods: Patients (n = 17) diagnosed with sleep apnea or primary snoring were included in this study and subsequently treated with MADs. Changes were assessed using a polysomnographic study (PSG), the Epworth Sleepiness Scale (ESS), and an imaging study with computed tomography scanning (CT). Studies were performed before and after the use of MAD. Anteroposterior measurements were taken in the sagittal plane at the hard palate, glottis, and supraglottic levels along the hard palate axis. Afterward, measurements were taken in the axial plane at the same levels along the hard palate axis. Results: From the six recorded measurements, the airway caliber increased by five. However, these changes were significant only in two measurements (sagittal hard palate and axial supraglottic). Snoring was controlled in 16 of the 17 subjects. From these sixteen, 12 subjects had a correct opening of the airway at the hard palate level. Moreover, daytime sleepiness decreased in all subjects. Discussion: Present results suggest that sagittal hard palate and axial supraglottic opening after use of MAD are mainly responsible for eliminating snoring and improve sleep apnea.

Rat dorsal prostate is necessary for vaginal adhesion of the seminal plug and sperm motility in the uterine horns.

The rat prostate comprises dorsal, ventral and lateral lobes that are morphologically and biochemically distinct. Lesions to these structures are expected to affect the quality of the ejaculate and male fertility. In experiment 1, we analyzed ejaculate parameters of males that had chemical lesions of the dorsal or ventral lobes. At pre-lesion and at 5 and 20 days post-lesion males were mated, and after ejaculation, seminal fluid and seminal plug were obtained from the mated females. In experiment 2, the ventral lobes were ablated, and the ejaculate was analyzed. In experiment 3, the fertility of males with chemically-lesioned dorsal lobes or ablation of the ventral lobes was evaluated. Chemical lesion of the dorsal lobe prevented the adhesion of the seminal plug to vaginal walls. When these males were tested at 5-days postlesion, no sperm were found in uterus, and at 20-days post-lesion, the few sperm encountered showed slow progressive motility. None of the females that mated with dorsal lobe-lesioned males became pregnant. However, chemical lesion or ablation of the ventral lobes did not affect ejaculate or fertility. Our results indicate that the dorsal prostatic lobes are indispensable for reproductive success in males, and define parameters of ejaculate with which fertility can be estimated.

How is the Epworth Sleepiness Scale related with subjective sleep quality and polysomnographic features in patients with sleep-disordered breathing?

PURPOSE: To determine the relationship between the Epworth Sleepiness Scale (ESS) and the Subjective Sleep Quality (SSQ) or polysomnographic (PSG) features in patients with sleep-disordered breathing (SDB). METHODS: This is a retrospective study that included 646 untreated patients with a PSG diagnosis of primary snoring (PS) or obstructive sleep apnea syndrome. Patients with SDB were grouped into four categories according to ESS scores: no diurnal sleepiness (DS) = 0-6; mild DS = 7-12; moderate DS = 13-18, and severe DS = ≥19. Analyses of variance were performed to compare SSQ or PSG features among the four ESS severity categories. RESULTS: We found a significant increase in subjective sleep time in the group of patients with severe DS. With regard to PSG data, we also identified increases in total sleep time (TST) and rapid eye movement (REM) in the group of patients with severe DS. CONCLUSION: Unexpectedly, DS severity was related with increases in TST and REM sleep. As has been described in SDB patients, a change in muscular tonus throughout sleep onset (and depth) is a causal factor of SDB features and DS impairment. Therefore, we propose that increases in TST and REM are worsening factors of SDB and consequently, also in DS.

[Sleep medicine: development, contributions and perspectives. Report of the work group on sleep medicine]. / Medicina del dormir: desarrollo, contribuciones y perspectivas. Reporte del grupo de trabajo en medicina del dormir.

Sleep is a basic biological process that has an impact on all the functions of the body, and interacts bidirectionally with virtually all of the body systems, so that the sleep disorders are associated with disturbances in other systems, either respiratory, neurological, cardiovascular, endocrine, immune, etc., and vice versa. The complexity of the regulatory mechanisms of sleep and the variety of their disorders, together with the clinical evidence accumulated in recent decades, have led to the birth of a new branch in medicine: the Sleep Medicine, with well defined intrinsic disorders. The consequences of sleep deprivation or fragmentation induced by changes in social and work dynamics, as well as sleep disorders have harmful effects on individuals in the short and long-term, the most important are an elevated risk for vehicular and occupational accidents, cardiovascular damage, cognitive impairment, obesity, diabetes mellitus, among others, impacting individuals of all ages. The sleep clinics and laboratories in Mexico, have made significant contributions, at both the basic and clinical levels, for the diagnosis and treatment of sleep disorders; however, without a specific health policy, we will continue to commit resources only on the attention of its effects and not on prevention, making the impact on the economy and quality of life of patients with sleep disorders, much higher than in developed countries. It is necessary to build a program of medical care to incorporate the Sleep Medicine in the priorities of medical care in the National Institutions of Health at all levels. Solutions and guides to optimize the achievement of the proposed results, and increase efficiency and effectiveness of the resources applied in this new field of Medicine are offered.

Sleep and Mental Health Disturbances Due to Social Isolation during the COVID-19 Pandemic in Mexico.

The coronavirus disease (COVID-19) that broke out in China in December 2019 rapidly became a worldwide pandemic. In Mexico, the conditions requiring the declaration of a sanitary emergency were reached by the last week of March 2020, and health authorities' limited mobility and imposed social isolation were the main strategies to keep the virus from spreading. Thus, daily living conditions changed drastically in a few days, generating a stressful situation characterized by an almost complete lack of mobility, social isolation, and forced full-time interactions with family members. Soon, complaints of sleep disturbances, anxiety, and symptoms of depression were reported. The present study reports the results of an online survey performed during the first two months of isolation. Questionnaires exploring sleep disturbances, anxiety, and depression were sent to people who responded to an open invitation. A total of 1230 participants filled out the sleep questionnaire, 812 responded to the anxiety questionnaire, and 814 responded to the depression questionnaire. Both men and women reported poor sleep quality, but women showed a higher proportion (79%) than men (60%); young women were more likely to be affected by social isolation. Concerning anxiety and depression, both sexes reported high similar symptoms. These data suggest that stressful conditions related to social isolation and the economic uncertainty caused by the pandemic may induce mental health disturbances, which may become worse with sleep restriction.

Metabolic Disturbances Induced by Sleep Restriction as Potential Triggers for Alzheimer's Disease.

Sleep has a major role in learning, memory consolidation, and metabolic function. Although it is known that sleep restriction increases the accumulation of amyloid ß peptide (Aß) and the risk to develop Alzheimer's disease (AD), the mechanism behind these effects remains unknown. In this review, we discuss how chronic sleep restriction induces metabolic and cognitive impairments that could result in the development of AD in late life. Here, we integrate evidence regarding mechanisms whereby metabolic signaling becomes disturbed after short or chronic sleep restriction in the context of cognitive impairment, particularly in the accumulation of Aß in the brain. We also discuss the role of the blood-brain barrier in sleep restriction with an emphasis on the transport of metabolic signals into the brain and Aß clearance. This review presents the unexplored possibility that the alteration of peripheral metabolic signals induced by sleep restriction, especially insulin resistance, is responsible for cognitive deficit and, subsequently, implicated in AD development.

Copulatory pattern of male rats in a multiple partner choice arena.

INTRODUCTION: It has been demonstrated that testing conditions may influence sexual performance in many mammals, including male rats. We recently developed a multiple partner choice arena (MPCA) consisting of four acrylic cylinders placed in a cross pattern with one male in each cylinder. A sexually receptive female rat was introduced into the center of the MPCA and was allowed to choose a male to copulate with. The female showed a preference for one of the four males, remaining longer and copulating more times with it. AIM: The study aims to evaluate and compare the copulatory pattern of male rats in two arenas: the standard arena (SA) and the MPCA. METHODS: In Experiment 1, a group of 10 male rats mated in an SA (a closed cylinder) and 2 weeks later they mated in the MPCA, in order to compare different parameters of male sexual behavior. In Experiment 2, the sexual behavior of two different groups of sexually experienced male rats was tested in two conditions: the SA and the MPCA. In the latter, only the behavior of the preferred (P) males and nonpreferred (NP) males that ejaculated was recorded. MAIN OUTCOME MEASURES: The main outcome is the number of intromissions preceding ejaculation and the latencies to mount, intromit, and ejaculate. RESULTS: In Experiment 1, the number of intromissions was significantly reduced and the intromission and ejaculation latencies were significantly shortened when the males were tested in the MPCA rather than in the SA. In Experiment 2, both groups of males tested in the MPCA (P and NP) showed a significant reduction in the number of intromissions preceding ejaculation and shorter mounting and ejaculation latencies in comparison with rats in the SA. This decrease was more noticeable in NP males. CONCLUSIONS: The MPCA reduce significantly the ejaculatory pattern in male rats.

The mild stress of chronic prenatal injections may have additive effects on drugs administered during pregnancy to alter brain sexual differentiation.

OBJECTIVE: In order to clarify the effect of the prenatal (PN) treatment of the drug 1,4,6-androstatriene-3,17-dione (ATD) which blocks the conversion of testosterone into estradiol on male sexual behavior of the rats offsprings, from the effect of the mild stress induced by the PN administration of the Propylene glycol (PG), the vehicle used to dissolve ATD. METHODS: Pregnant Wistar rats were divided into three groups. The CON group did not receive any kind of treatment. The other two groups (PG and ATD) were injected i.p. during gestation (days 11-22) with 0 and 5 mg of ATD, dissolved in 0.1 ml of PG, respectively, doses reported by other authors. Sexual performance of the male pups was analyzed three months later in four successive tests. RESULTS: In the first sexual test of these naive rats, the percentage of males mounting, intromitting, ejaculating and the ejaculation frequency of the ATD group decreased significantly in comparison with the CON group. Also in the first and 4th tests, mounting, intromission and ejaculation latencies, as in the post-ejaculatory refractory period, ATD group, was significantly longer in comparison with the CON group. PG males showed a male sexual behavior (MSB) similar to that observed in the ATD group, but the differences did not reach statistical significance when they were compared with the CON group. CONCLUSION: We considered that the PN stress induced by the daily administration of PG and ATD, results in a slower execution of the MSB in both groups and avoid distinguish the effect of the ATD. Then chronic PN injections, as a route of administration, could act as mild stressor and may have additive effects on drugs affecting brain sexual differentiation.

Diverse sleep patterns, psychiatric disorders, and perceived stress in inhalants users living on the streets of Mexico City.

Homeless people face stressful circumstances influencing drug consumption, mental health, and sleep disorders. We performed an interdisciplinary study involving psychometric, polysomnographic, and ethnographic records to relate stress, psychiatric disorders, drug consumption, and sleep in ten people (four women, M = 32 y/o) living on the streets of Mexico City. Toluene-based inhalant dependence and suicidality were the more common psychiatric disorders among participants. They also presented sleep fragmentation; some manifested insomnia or sleep restriction, whereas others displayed extended rapid-eye movement sleep latencies associated with depression or inhalant consumption. Inhalants are used to improve mood, strengthen social bonds, and induce either sleep or alertness during the night. Inter-individual distinctions may be related to differential levels of intoxication, stress perception, backgrounds, and abilities to live and sleep on the street. Sleep restriction seems to be the more common factor, which may enhance the negative consequences of street situation.

Cyclic alternating pattern in infants with congenital hypothyroidism.

Congenital hypothyroidism is defined as thyroid hormone deficiency present at birth which is crucial for brain development. Recently, the cyclic alternating pattern, a rhythm present in electroencephalography recordings in non-Rapid eye movement sleep, has been related to brain development and cognition in different pediatric conditions. Therefore, we evaluated the cyclic alternating pattern rate in infants with congenital hypothyroidism, thyroxine supplementation, and healthy controls. The parameters of the cyclic alternating pattern were evaluated in 19 healthy infants (10 female, mean age 25.5 ±â€¯15.5 months) and 21 infants diagnosed with congenital hypothyroidism (19 female, mean age 24.3 ±â€¯19.0 months). We considered the transient electro-cortical activations (phase A of the cycle) in non-Rapid eye movement sleep and the subdivisions of the A phase in: A1, A2 and A3, based on their frequency content. All subjects were subjected to polysomnography recording in a standard laboratory setting. Sleep data were stored computer following the International 10-20 System. Data showed that congenital hypothyroidism infants exhibited higher frequency of central apnea, hypopnea, and arousals in comparison to controls. Particularly, central apnea index decreased with age in the control group but not in congenital hypothyroidism group. Regarding to cyclic alternating pattern measurements, congenital hypothyroidism infants exhibit a higher frequency in the percentage of A3 subtype (electroencephalographic desynchrony) and conversely a lower percentage of A1 subtype (electroencephalographic synchrony), than healthy infants. An important finding of this study is the positive correlation between A1 mean duration and age, which is bigger in control group than in congenital hypothyroidism group (time duration in control group (0.52 s/month) versus congenital hypothyroidism group (0.1 s/month). Infants with congenital hypothyroidism showed an increase of A3 subtype, of central apnea, and of arousals. The reduction of percentage and mean duration of A1 subtype could be a valuable indicator of sleep development in patients with congenital hypothyroidism and healthy infants.

Sleep-EEG patterns of school children suffering from symptoms of depression compared to healthy controls.

Depression in children is often an elusive disorder and its diagnostic tools are a matter of controversy. Several scales have been developed in an attempt to specifically detect some of the major aspects of depression, i.e. anhedonia, sadness, hopelessness. On the other hand, in adults depression frequently induces changes in sleep patterns, particularly a shortening in REM sleep latency. The alteration of sleep patterns in depressed children has been a matter of controversy. It is possible that a diagnostic deficiency might be the source of the contradictory reports. In the present study, The Child Depression Inventory, a rating scale specifically developed for child depression was applied to 396 school children (8-12 years of age). Nearly 15% of the children (N = 45) obtained scores higher than the established limit in this test for normal healthy subjects. A sample of children found within the highest (N = 25) and within the lowest (N = 25) scores in the scale were selected. After a clinical evaluation, only those who meet the inclusion criteria (N = 21 for depressed and N = 7 for healthy controls) were electroencephalographically recorded. Children with depressive symptoms showed a significant shortening in REM sleep latency (mean = 108 min) when compared to non-depressed (mean = 150 min). In addition, significant increases were observed in sleep latency, REM sleep duration and the number of awakenings. Furthermore, results showed an unexpected high frequency of EEG abnormalities in children with depressive symptoms (75%) characterized by sharp waves and polyspikes in the frontal region. The present results support the notion that depression, in children, is accompanied by changes in sleep patterns, mainly concerning REM sleep.

Postnatal overnutrition alters the orexigenic effects of melanin-concentrating hormone (MCH) and reduces MCHR1 hypothalamic expression on spontaneous feeding and fasting.

One of the approaches to induce obesity in rodents consists in reducing litter size to 3 pups during the lactation period. Animals submitted to this manipulation are heavier, hyperphagic and develop several metabolic diseases for the rest of their lives. In the present study, under the premise that melanin-concentrating hormone (MCH), an orexigenic peptide synthesized by neurons of the lateral hypothalamus, is involved in food intake regulation, we aimed to measure the hypothalamic expression of its receptor, MCHR1, in adult early overfed obese animals and normoweight controls at both ad libitum and food deprived conditions. Additionally, we administered MCH, or an antiMCH antibody, into the third ventricle of ad libitum-fed rats, or fasted rats, respectively, and evaluated chow consumption. Typical nocturnal hyperphagia in rodents was elevated in obese animals compared to normoweight controls, accompanied by a lower expression of MCHR1 and leptin receptor (Ob-R). Following a 24 h fasting, MCHR1 remained lower in SL rats. After 4 h of re-feeding, obese animals ate more than normoweight controls. MCH failed to enhance appetite in early overfed obese animals and immunoneutralization of the peptide only reduced fasted induced-hyperphagia in normoweight controls. These results support the notion that both peptide and brain endogenous MCH exert a physiological relevant action in food intake regulation in normoweight rats, but that postnatal overnutrition disturbs this system, as reflected by MCHR1 downregulation at both ad libitum and fasted conditions and in the lack of response to MCH in both positive- and negative-energetic states in early overfed obese animals.