Methadone administered to rat dams during pregnancy and lactation affects the circadian rhythms of their pups.

The circadian clock is one of the most important homeostatic systems regulating the majority of physiological functions. Its proper development contributes significantly to the maintenance of health in adulthood. Methadone is recommended for the treatment of opioid use disorders during pregnancy, increasing the number of children prenatally exposed to long-acting opioids.

Circadian control of kynurenine pathway enzymes in the rat pineal gland, liver, and heart and tissue- and enzyme-specific responses to lipopolysaccharide.

Amino acid tryptophan is catabolised via the kynurenine and serotonin-melatonin pathways, leading to various biologically active metabolites involved in regulating immunity, metabolism, and neuronal function. The levels of these metabolites are determined by the enzymes, which respond to altered homeostasis and pathological processes in the body. For the pineal gland, most work has centred on the serotonin-melatonin pathway.

Circadian rhythms of locomotor activity in rats: Data on the effect of morphine administered from the early stages of embryonic development until weaning.

The circadian clock generates behavioural and physiological rhythms to maximize the efficacy of organismal functions. The circadian system with a major circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus develops gradually and its proper function in adulthood depends on an appropriate neurochemical milieu during ontogeny [1]. Locomotor activity is under direct control by the circadian clock, and alterations in its rhythmicity indicate changes of circadian clock function.

Maternal morphine intake during pregnancy and lactation affects the circadian clock of rat pups.

Early-life morphine exposure causes a variety of behavioural and physiological alterations observed later in life. In the present study, we investigated the effects of prenatal and early postnatal morphine on the maturation of the circadian clockwork in the suprachiasmatic nucleus and the liver, and the rhythm in aralkylamine N-acetyltransferase activity in the pineal gland. Our data suggest that the most affected animals were those born to control, untreated mothers and cross-fostered by morphine-exposed dams.

Circadian Regulation of GluA2 mRNA Processing in the Rat Suprachiasmatic Nucleus and Other Brain Structures.

The mammalian circadian system consists of a major circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks in the body, including brain structures. The SCN depends on glutamatergic neurotransmission for transmitting signals from the retina, and it exhibits spontaneous 24-h rhythmicity in neural activity. The aim of this work was to evaluate the degree and circadian rhythmicity of AMPA receptor GluA2 subunit R/G editing and alternative flip/flop splicing in the SCN and other brain structures in Wistar rats.

Prenatal exposure to lipopolysaccharide induces changes in the circadian clock in the SCN and AA-NAT activity in the pineal gland.

The mammalian circadian pacemaker in the suprachiasmatic nucleus (SCN) regulates behavioral and physiological processes in a 24-h cycle. During its development, the SCN can be sensitive to external stimuli which may change the circadian phenotypes in adulthood. Here, we investigated the effects of prenatal exposure to endotoxin lipopolysaccharide (LPS) on the developing rhythms in expression of Per1, Per2, Nr1d1 and Rasd1 along the rostrocaudal axis of the SCN, and on the rhythm of the rate-limiting enzyme in melatonin synthesis, pineal alkylamine N-acetyltransferase (AA-NAT).

Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABA and GABA Receptors.

Benzodiazepines (BZDs) are widely used in patients of all ages. Unlike adults, neonatal animals treated with BZDs exhibit a variety of behavioral deficits later in life; however, the mechanisms underlying these deficits are poorly understood. This study aims to examine whether administration of clonazepam (CZP; 1 mg/kg/day) in 7-11-day-old rats affects Gama aminobutyric acid (GABA)ergic receptors in both the short and long terms.

Social defeat stress affects resident's clock gene and expression in the brain.

Social defeat stress affects behavior and changes the expression of the genes underlying neuronal plasticity in the brain. The circadian clock regulates most neuronal processes in the brain, which results in daily variations of complex behavior, and any disturbance in circadian clock oscillations increases the risk of mood and cognitive disbalance. In this study, we assessed the effect of acute and repeated social defeat stress on and expression in prefrontal cortexes, hippocampi, pineal glands, olfactory bulbs, cerebella, and pituitary glands.

The day-night differences in ERK1/2, GSK3β activity and c-Fos levels in the brain, and the responsiveness of various brain structures to morphine.

As with other drugs or pharmaceuticals, opioids differ in their rewarding or analgesic effects depending on when they are applied. In the previous study, we have demonstrated the day/night difference in the sensitivity of the major circadian clock in the suprachiasmatic nucleus to a low dose of morphine, and showed the bidirectional effect of morphine on pERK1/2 and pGSK3β levels in the suprachiasmatic nucleus depending on the time of administration. The main aim of this study was to identify other brain structures that respond differently to morphine depending on the time of its administration.

The effect of the cannabinoid receptor agonist and antagonist on the light-induced changes in the suprachiasmatic nucleus of rats.

The CB1 cannabinoid receptors have been found in the rodent suprachiasmatic nucleus, and their activation suppresses the light-induced phase shift in locomotor rhythmicity of mice and hamsters. Here, we show that the CB1 receptor agonist CP55940 significantly attenuates the light-induced phase delay in rats as well. Furthermore, it blocks the light induction of c-Fos and light-induced downregulation of pERK1/2 in the SCN, and the CB1 antagonist AM251 prevents the photic induction of pERK1/2 and reduces pGSK3β after photic stimulation.

Neonatal Clonazepam Administration Induces Long-Lasting Changes in Glutamate Receptors.

γ-aminobutyric acid (GABA) pathways play an important role in neuronal circuitry formation during early postnatal development. Our previous studies revealed an increased risk for adverse neurodevelopmental consequences in animals exposed to benzodiazepines, which enhance GABA inhibition via GABA receptors. We reported that administration of the benzodiazepine clonazepam (CZP) during postnatal days 7-11 resulted in permanent behavioral alterations.

The day/night difference in the circadian clock's response to acute lipopolysaccharide and the rhythmic Stat3 expression in the rat suprachiasmatic nucleus.

The circadian clock in the suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behaviour and is an important part of the mammalian homeostatic system. Previously, we have shown that systemic inflammatory stimulation with lipopolysaccharide (LPS) induced the daytime-dependent phosphorylation of STAT3 in the SCN. Here, we demonstrate the LPS-induced Stat3 mRNA expression in the SCN and show also the circadian rhythm in Stat3 expression in the SCN, with high levels during the day.

Circadian Dexras1 in rats: Development, location and responsiveness to light.

Dexras1 has been shown to exhibit clock-dependent rhythm in mice suprachiasmatic nucleus (SCN), and its genetic deletion modulates circadian responses to photic and nonphotic cues. We show that the rhythmic expression of Dexras1 mRNA and protein in rat SCN already oscillates with low amplitude at postnatal day 3 and can be detected as early as embryonic day 20. In contrast, its expression in peripheral tissues is not rhythmic in adult rats either.

Identification of STAT3 and STAT5 proteins in the rat suprachiasmatic nucleus and the Day/Night difference in astrocytic STAT3 phosphorylation in response to lipopolysaccharide.

Signal transducers and activators of transcription (STAT) proteins regulate many aspects of cellular physiology from growth and differentiations to immune responses. Using immunohistochemistry, we show the daily rhythm of STAT3 protein in the rat suprachiasmatic nucleus (SCN), with low but significant amplitude peaking in the morning. We also reveal the strong expression of STAT5A in astrocytes of the SCN and the STAT5B signal in nonastrocytic cells.

Delayed Effect of the Light Pulse on Phosphorylated ERK1/2 and GSK3β Kinases in the Ventrolateral Suprachiasmatic Nucleus of Rat.

The intrinsic period of circadian clock in the suprachiasmatic nucleus is entrained to a 24-h cycle by external cues, mainly light. Previous studies have shown that light applied at night induces robust phosphorylation of extracellular-signal-regulated kinase that is necessary to process the light pulse into the phase shift of the clock phase. In this study, we show the persistent downregulation of phosphorylated extracellular-signal-regulated kinase and transient downregulation of phosphorylated glycogen synthase kinase-3beta in the ventrolateral part of the suprachiasmatic nucleus to photic stimuli starting at 2 h after the beginning of the light pulse.

Acute morphine affects the rat circadian clock via rhythms of phosphorylated ERK1/2 and GSK3β kinases and Per1 expression in the rat suprachiasmatic nucleus.

Background And Purpose: Opioids affect the circadian clock and may change the timing of many physiological processes. This study was undertaken to investigate the daily changes in sensitivity of the circadian pacemaker to an analgesic dose of morphine, and to uncover a possible interplay between circadian and opioid signalling.

Experimental Approach: A time-dependent effect of morphine (1 mg·kg(-1) , i.