Brain serotonin turnover and plasma prolactin and growth hormone concentrations during changes in osmotic balance in the domestic fowl

Summary Young cockerels injected 24 h earlier with 0.9% saline,para-chorophenylalanine (pCPA, brain serotonin depletor) or alpha-methylpara-tyrosine (AMPT, brain catecholamine depletor) were deprived of access to water for 24 h. Plasma prolactin concentrations were markedly elevated by water deprivation and returned to normal on rehydration. pCPA, but not AMPT, significantly reduced the increase in prolactin. Concentrations of growth hormone were not affected by water deprivation. Brain serotonin concentrations were reduced by treatment with pCPA. Groups of cockerels were maintained under normal conditions or without access to drinking water for 12 h or 24h. Some were injected with the monoamine oxidase inhibitor pargyline, which increased the prolactin and decreased the growth hormone concentration in the plasma of the hydrated birds. The inhibitory effect of pargyline on growth hormone was augmented following water deprivation. Serotonin levels were not significantly affected by water deprivation but turnover (defined as accumulation of serotonin after pargyline treatment) was increased in the hypothalamus but not in remaining tissue. Injecting 30% saline solution intravenously markedly increased plasma prolactin whilst growth hormone concentrations were decreased. Serotonin turnover was increased in the hypothalamus but not in other brain regions. The results show that secretion of prolactin and growth hormone by the pituitary gland during osmotic imbalance in the fowl may be mediated by changes in hypothalamic scrotonin turnover.     

Brain prolactin is involved in stress-induced REM sleep rebound

REM sleep rebound is a common behavioural response to some stressors and represents an adaptive coping strategy. Animals submitted to multiple, intermittent, footshock stress (FS) sessions during 96 h of REM sleep deprivation (REMSD) display increased REM sleep rebound (when compared to the only REMSD ones, without FS), which is correlated to high plasma prolactin levels. To investigate whether brain prolactin plays a role in stress-induced REM sleep rebound two experiments were carried out. In experiment 1, rats were either not sleep-deprived (NSD) or submitted to 96 h of REMSD associated or not to FS and brains were evaluated for PRL immunoreactivity (PRL-ir) and determination of PRL concentrations in the lateral hypothalamus and dorsal raphe nucleus. In experiment 2, rats were implanted with cannulas in the dorsal raphe nucleus for prolactin infusion and were sleep-recorded. REMSD associated with FS increased PRL-ir and content in the lateral hypothalamus and all manipulations increased prolactin content in the dorsal raphe nucleus compared to the NSD group. Prolactin infusion in the dorsal raphe nucleus increased the time and length of REM sleep episodes 3 h after the infusion until the end of the light phase of the day cycle. Based on these results we concluded that brain prolactin is a major mediator of stress-induced REMS. The effect of PRL infusion in the dorsal raphe nucleus is discussed in light of the existence of a bidirectional relationship between this hormone and serotonin as regulators of stress-induced REM sleep rebound.     

Effects of selective sleep deprivation on ventilation during recovery sleep in normal humans.

To assess the effects of selective sleep loss on ventilation during recovery sleep, we deprived 10 healthy young adult humans of rapid-eye-movement (REM) sleep for 48 h and compared ventilation measured during the recovery night with that measured during the baseline night. At a later date we repeated the study using awakenings during non-rapid-eye-movement (NREM) sleep at the same frequency as in REM sleep deprivation. Neither intervention produced significant changes in average minute ventilation during presleep wakefulness, NREM sleep, or the first REM sleep period. By contrast, both interventions resulted in an increased frequency of breaths, in which ventilation was reduced below the range for tonic REM sleep, and in an increased number of longer episodes, in which ventilation was reduced during the first REM sleep period on the recovery night. The changes after REM sleep deprivation were largely due to an increase in the duration of the REM sleep period with an increase in the total phasic activity and, to a lesser extent, to changes in the relationship between ventilatory components and phasic eye movements. The changes in ventilation after partial NREM sleep deprivation were associated with more pronounced changes in the relationship between specific ventilatory components and eye movement density, whereas no change was observed in the composition of the first REM sleep period. These findings demonstrate that sleep deprivation leads to changes in ventilation during subsequent REM sleep.     

Noradrenaline acting on alpha1-adrenoceptor mediates REM sleep deprivation-induced increased membrane potential in rat brain synaptosomes

We hypothesized that one of the functions of REM sleep is to maintain brain excitability and therefore, REM sleep deprivation is likely to modulate neuronal transmembrane potential; however, so far there was no direct evidence to support the claim. In this study a cationic dye, 3,3'-diethylthiacarbocyanine iodide was used to estimate the potential in synaptosomal samples prepared from control and REM sleep deprived rat brains. The activity of Na-K-ATPase that maintains the transmembrane potential was also estimated in the same sample. Further, the roles of noradrenaline and alpha1-adrenoceptor in mediating the responses were studied both in vivo as well as in vitro. Rats were REM sleep deprived for 4 days by the classical flower-pot method; large platform and recovery controls were carried out in addition to free-moving control. The fluorescence intensity increased in samples prepared from REM sleep deprived rat brain as compared to control, which reflected synaptosomal depolarization after deprivation. The Na-K-ATPase activity also increased in the same deprived sample. Furthermore, both the effects were mediated by noradrenaline acting on alpha1-adrenoceptors in the brain. This is the first direct evidence showing that REM sleep deprivation indeed increased neuronal depolarization, which is the likely cause for increased brain excitability, thus supporting our hypothesis and the effect was mediated by noradrenaline acting through the alpha1-adrenoceptor.     

Dopaminergic system in the telencephalic and diencephalic brain regions in vertebrates in the sleep-wakefulness cycle organisation

The aim of our study was to investigate the role of dopaminergic system in telencephalic and diencephalic brain regions of vertebrates in sleep-wakefulness cycle. The level of thyrosine-hydroxylase--the main enzyme in dopamine synthesis--was measured in striatum, zona inserta supraoptic and arcuate nuclea of hypothalamus in fish (Acipenceridae) and in mammals (rats) in ontogenesis (14-, 30-day old rats and adult animals) under tactile and sleep deprivation stresses. The thyrosine-hydroxylase-immunoreactive cells were revealed in all brain regions of fishes after a short-term stress. In the group after longtime stress, the thyrosine-hydroxylase-immunoreactive cells and fibers were almost absent in anterior brain but were found in hypothalamic nuclea. At 14-day old rats, 2-hour sleep deprivation caused increasing of thyrosine-hydroxylase-immunoreactivity both in fibers of caudate nucleus as well as in cells of the zona inserta. A 6-hour deprivation caused increasing of thyrosine-hydroxylase-immunoreactive material level in cells of zona inserta and decreasing it in fibers of 30-day old rats. In adult rats, the level of thyrosine-hydroxylase-immunoreactive material decreased in nucleus arcuatus and zona inserta after sleep deprivation and increased after sleep. Data obtained are discussed in terms ofphylo- and ontogenetic development of neurosecretory and neurotransmitter functions of dopaminergic system in evolutionary old diencephalic and evolutionary young telencephalic brain regions of vertebrates, which are the important systems of starting and maintenance of some functional conditions of the organism in sleep-wakefulness cycle.     

Selective REM sleep deprivation during daytime I. Time course of interventions and recovery sleep

Although repeated selective rapid eye movement (REM) sleep deprivation by awakenings during nighttime has shown that the number of sleep interruptions required to prevent REM sleep increases within and across consecutive nights, the underlying regulatory processes remained unspecified. To assess the role of circadian and homeostatic factors in REM sleep regulation, REM sleep was selectively deprived in healthy young adult males during a daytime sleep episode (7-15 h) after a night without sleep. Circadian REM sleep propensity is known to be high in the early morning. The number of interventions required to prevent REM sleep increased from the first to the third 2-h interval by a factor of two and then leveled off. Only a minor REM sleep rebound (11.6%) occurred in the following undisturbed recovery night. It is concluded that the limited rise of interventions during selective daytime REM sleep deprivation may be due to the declining circadian REM sleep propensity, which may partly offset the homeostatic drive and the sleep-dependent disinhibition of REM sleep.     

Chronic REM Sleep Restriction in Juvenile Male Rats Induces Anxiety-Like Behavior and Alters Monoamine Systems in the Amygdala and Hippocampus

Adolescence is marked by major physiological changes, including those in the sleep-wake cycle, such as phase delay, which may result in reduced sleep hours. Sleep restriction and/or deprivation in adult rats activate stress response and seem to be a risk factor for triggering emotional disorders. In the present study, we sought to evaluate the behavioral and neurobiological consequences of prolonged REM sleep restriction in juvenile male rats. Immediately after weaning, on postnatal day 21, three males from each litter were submitted to REM sleep deprivation and the other three animals were maintained in their home-cages. REM sleep restriction (REMSR) was accomplished by placing the animals in the modified multiple platform method for 18 h and 6 h in the home-cage, where they could sleep freely; the sleep restriction lasted 21 consecutive days, during which all animals were measured and weighed every 3 days. After the end of this period, all animals were allowed to sleep freely for 2 days, and then the behavioral tests were performed for evaluation of depressive and anxiety-like profiles (sucrose negative contrast test and elevated plus maze, EPM). Blood sampling was performed 5 min before and 30 and 60 min after the EPM for determination of corticosterone plasma levels. The adrenals were weighed and brains collected and dissected for monoamine levels and receptor protein expression. REMSR impaired the physical development of adolescents, persisting for a further week. Animals submitted to REMSR exhibited higher basal corticosterone levels and a greater anxiety index in the EPM, characteristic of an anxious profile. These animals also exhibited higher noradrenaline levels in the amygdala and ventral hippocampus, without any change in the expression of β1-adrenergic receptors, as well as higher serotonin and reduced turnover in the dorsal hippocampus, with diminished expression of 5-HT1_A. Finally, greater concentration of BDNF was observed in the dorsal hippocampus in chronically sleep-restricted animals. Chronic REMSR during puberty impaired physical development and induced anxiety-like behavior, attributed to increased noradrenaline and serotonin levels in the amygdala and hippocampus.     

Rapid eye movement (rem) sleep deprivation: effect on acid mucopolysaccharides in rat brain.

The effect of rapid eye movement (REM) sleep deprivation on the total content and proportion of different mucopolysaccharides (AMPS) containing uronic acid in rat brain was studied. REM sleep deprivation was induced by the water tank methods. Five experimental groups of animals were used: control, stressed, REM sleep deprived, post-stress sleeping and post-deprivation sleeping rats. No changes of AMPS were observed in any of the experimental groups when the whole brain was analysed. A significant increase of AMPS was found in the cerebral hemispheres of stressed and REM deprived rats. A significant decrease of AMPS was observed in the cerebellum and brain stem. A further increase of AMPS was found in the cerebral hemispheres after the rebound of REM sleep following its deprivation, and after the recovery sleep following the stress. A significant increase of AMPS was found in the brain stem of rats allowed to recuperate after REM deprivation or stress as compared with the stressed and REM deprived animals. Recovery sleep induced a significant increase of AMPS in the cerebellum in previously stressed rats, while previously REM deprived rats exhibited a further decrease of AMPS from control values. The possible functional meaning of these results is discussed in relation to the role of REM sleep in protein synthesis and learning and memory processes. Intriguing, well-controlled positive findings and the fact that no experimental design is known where stress is minimal while REM deprivation is 100 per cent, justify and encourage continued efforts in studying the biochemical state of the brain during sleep and/or its alterations.     

Circadian and sleep-deprivation variations of monophosphorylated MAP-Kinase in hypothalamus and pons of rats

Behavior and physiological changes are under the influence of circadian and homeostatic variations. Temporal alignment regulates timing of neurobiological phenomena, such as protein phosphorylation. In the current report, we describe the circadian and sleep homeostatic phosphorylated mitogen-activated protein kinase (MAP-K) variations in hypothalamus and pons of rats across 24 h as well as after sleep deprivation. In the circadian study, MAP-K expression showed a building-up profile during the dark phase in hypothalamus, whereas an increase across the lights-on period was found in pons. On the other hand, that phosphorylation of MAP-K in hypothalamus and pons displayed a significant reduction after sleep rebound period. Data demonstrate that MAP-K phosphorylation undergoes circadian and sleep homeostatic variations in brain areas linked to sleep modulation.     

Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats

The histamine-containing posterior hypothalamic region (PH-TMN) plays a key role in sleep-wake regulation. We investigated rapid changes in glutamate release in the PH-TMN across the sleep-wake cycle with a glutamate biosensor that allows the measurement of glutamate levels at 1- to 4-s resolution. In the PH-TMN, glutamate levels increased in active waking (AW) and rapid eye movement (REM) sleep compared with quiet waking and nonrapid eye movement (NREM) sleep. There was a rapid (0.6 +/- 1.8 s) and progressive increase in glutamate levels at REM sleep onset. A reduction in glutamate levels consistently preceded the offset of REM sleep by 8 +/- 3 s. Short-duration sleep deprivation resulted in a progressive increase in glutamate levels in the PH-TMN, perifornical-lateral hypothalamus (PF-LH), and cortex. We found that in the PF-LH, glutamate levels took a longer time to return to basal values compared with the time it took for glutamate levels to increase to peak values during AW onset. This is in contrast to other regions we studied in which the return to baseline values after AW was quicker than their rise with waking onset. In summary, we demonstrated an increase in glutamate levels in the PH-TMN with REM/AW onset and a drop in glutamate levels before the offset of REM. High temporal resolution measurement of glutamate levels reveals dynamic changes in release linked to the initiation and termination of REM sleep.     

The dynamics of spindles and EEG slow-wave activity in NREM sleep in mice

A quantitative analysis of spindles and spindle-related EEG activity was performed in C57BL/6 mice. The hypothesis that spindles are involved in sleep regulatory mechanisms was tested by investigating their occurrence during 24 h and after 6 h sleep deprivation (SD; n = 7). In the frontal derivation distinct spindle events were characterized as EEG oscillations with a dominant frequency approximately at 11 Hz. Spindles were most prominent during NREM sleep and increased before NREM-REM sleep transitions. Whereas spindles increased concomitantly with slow wave activity (SWA, EEG power between 0.5 and 4.0 Hz) at the beginning of the NREM sleep episode, these measures showed an opposite evolution prior to the transition to REM sleep. The 24-h time course of spindles showed a maximum at the end of the 12-h light period, and was a mirror image of SWA in NREM sleep. After 6 h SD the spindles in NREM sleep were initially suppressed, and showed a delayed rebound. In contrast, spindles occurring immediately before the transition to REM sleep were enhanced during the first 2 h of recovery. The data suggest that spindles in NREM sleep may be involved in sleep maintenance, while spindles heralding the transition to REM sleep may be related to mechanisms of REM sleep initiation.     

Cardiopulmonary regulation after rapid-eye-movement sleep deprivation.

Arterial blood pressure, chest movement, electroencephalogram, and electromyogram were monitored in six normotensive Sprague-Dawley rats for 4 h/day 3 days before and 4 days after 114 h of rapid-eye-movement (REM) sleep deprivation. During recovery sleep immediately after REM sleep deprivation (RD), there was a significant increase in the amount of time spent in REM sleep. During this rebound in REM sleep, there was a significant rise (26%) in heart rate in wakefulness, non-REM sleep, and REM sleep during the first 4 h after RD. Systolic blood pressure was also significantly elevated (14%) but only during wakefulness before recovery sleep. Rats with the greatest waking systolic blood pressure after RD had the lowest REM sleep rebound in the 4 h immediately after RD (r = -0.885, P less than 0.05). The rise in heart rate, systolic blood pressure, and REM sleep time evident on day 1 immediately after RD was absent on recovery days 2-4. The respiratory rate tended to be higher throughout the recovery period in every state of consciousness; however, these values never reached the level of significance. In the initial recovery sleep period, regulation of heart rate was more disrupted by REM sleep deprivation than either arterial blood pressure or respiratory rate.     

Coupled Flip-Flop Model for REM Sleep Regulation in the Rat

Recent experimental studies investigating the neuronal regulation of rapid eye movement (REM) sleep have identified mutually inhibitory synaptic projections among REM sleep-promoting (REM-on) and REM sleep-inhibiting (REM-off) neuronal populations that act to maintain the REM sleep state and control its onset and offset. The control mechanism of mutually inhibitory synaptic interactions mirrors the proposed flip-flop switch for sleep-wake regulation consisting of mutually inhibitory synaptic projections between wake- and sleep-promoting neuronal populations. While a number of synaptic projections have been identified between these REM-on/REM-off populations and wake/sleep-promoting populations, the specific interactions that govern behavioral state transitions have not been completely determined. Using a minimal mathematical model, we investigated behavioral state transition dynamics dictated by a system of coupled flip-flops, one to control transitions between wake and sleep states, and another to control transitions into and out of REM sleep. The model describes the neurotransmitter-mediated inhibitory interactions between a wake- and sleep-promoting population, and between a REM-on and REM-off population. We proposed interactions between the wake/sleep and REM-on/REM-off flip-flops to replicate the behavioral state statistics and probabilities of behavioral state transitions measured from experimental recordings of rat sleep under ad libitum conditions and after 24 h of REM sleep deprivation. Reliable transitions from REM sleep to wake, as dictated by the data, indicated the necessity of an excitatory projection from the REM-on population to the wake-promoting population. To replicate the increase in REM-wake-REM transitions observed after 24 h REM sleep deprivation required that this excitatory projection promote transient activation of the wake-promoting population. Obtaining the reliable wake-nonREM sleep transitions observed in the data required that activity of the wake-promoting population modulated the interaction between the REM-on and REM-off populations. This analysis suggests neuronal processes to be targeted in further experimental studies of the regulatory mechanisms of REM sleep.     

Tyrosine hydroxylase activity in rat brain following "REM" sleep deprivation

I n R ecent years biogenic amines have been implicated in the control mechanism for induction and maintenance of sleep processes (J ouvet , 1969). Investigators have looked for changes in the rate of synthesis of cerebral norepinephrine from [³H]tyrosine after REM sleep deprivation and reported increased rates of synthesis during REM sleep deprivation (M ark , H einer , M andel and G odin , 1969) and REM sleep rebound following 91 h of deprivation (P ujol , M ouret and G lowinski , 1968). Because tyrosine is thought to be the rate-limiting enzyme (U denfriend , 1966) in the synthetic pathways for norepinephrine and since the above-mentioned studies are suggestive of changes in the activity of the enzyme, we decided to measure tyrosine hydroxylase activity following REM sleep deprivation.     

Dose-dependent dual effect of corticosterone on cerebral 5-HT metabolism

The action of 1.0 and 10.0 mg/kg (i.p.) of corticosterone on serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents and on serotonin turnover, measured by an MAO-inhibitor method, was studied at 30 and 120 min after administration. A 1.0 mg/kg dose of corticosterone increased the serotonin content and turnover in the hypothalamus and mesencephalon 30 min after administration; however, it was ineffective on dorsal hippocampus and frontal and parietal cortex. 5-HIAA content did not change significantly in any of the brain areas studied. A 10.0 mg/kg dose of corticosterone decreased the serotonin content and turnover in the hypothalamus and mesencephalon; it was ineffective in other brain areas investigated. 5-HIAA content significantly decreased in the hypothalamus while it increased in the mesencephalon and dorsal hippocampus. In the parietal and frontal cortex, 5-HIAA content did not change following administration of 10.0 mg/kg of corticosterone. At 120 min after corticosterone administration, neither 5-HT content and turnover nor 5-HIAA content showed any change in the brain areas investigated. The results suggest that corticosteroids might change the activity of the brain serotoninergic system in a dose- and time-dependent manner, and in this way the serotoninergic system might play an important role in mediation of the corticosteroid effect exerted on brain function.     

Sleep EEG spectral analysis in a diurnal rodent:Eutamias sibiricus

1. Sleep was studied in the diurnal rodent Eutamias sibiricus, chronically implanted with EEG and EMG electrodes. Analysis of the distribution of wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep over the 24 h period (LD 12:12) showed that total sleep time was 27.5% of recording time during the 12 h light period and 74.4% during the 12 h dark period. Spectral analysis of the sleep EEG revealed a progressive decay in delta power density in NREM sleep during darkness. Power density of the higher frequencies increased at the end of darkness. Power density of the higher frequencies decreased and that of the lower frequencies increased during light. 2. Analysis of the distribution of vigilance states under three different photoperiods (LD 18:6; 12:12; 6:18) revealed that changes in daylength mainly resulted in a redistribution of sleep and wakefulness over light and darkness. Under long days the percentage of sleep during light was enhanced. The time course of delta power density in NREM sleep was characterized by a long rising part and a short falling part under long days, while a reversed picture emerged under short days. As a consequence, the power density during days. As a consequence, the power density during light was relatively high under long days. 3. After 24 h sleep deprivation by forced activity, no significant changes in the percentages of wakefulness and NREM were observed, whereas REM sleep was slightly enhanced. EEG power density, however, was significantly increased by ca. 50% in the 1.25-10.0 Hz range in the first 3 h of recovery sleep. This increase gradually decayed over the recovery night. 4. The same 24 h sleep deprivation technique led to a ca. 25% increase in oxygen consumption during recovery nights. While the results of the EEG spectral analysis are compatible with the hypothesis that delta power density reflects the 'intensity' of NREM sleep as enhanced by prior wakefulness and reduced by prior sleep, such enhanced sleep depth after sleep deprivation is not associated with reduced energy expenditure as might be anticipated by some energy conservation hypotheses on sleep function.     

Control of REM sleep: an aspect of the regulation of physiological homeostasis.

Since REM sleep is characterized by a suspension of the hypothalamic integration of homeostatic regulations, it has been assumed that the duration of both REM sleep episodes and of the time interval between the end of one episode and the beginning of the following episode may be regulated according to sleep related processes and the homeostatic needs of the organism. A series of studies performed on the rat has shown that REM sleep episodes occur as two basic types: single REM sleep episodes, that are separated by intervals > 3 min and sequential episodes, that are separated by intervals < or = 3 min and appear in a cluster. Moreover, it has been observed that, in this species, a change in REM sleep occurrence is caused by a modification in the number of episodes and not in their duration. With respect to this, sleep deprivation and recovery are characterized by a decrease and an increase, respectively, in the number of sequential REM sleep episodes, but the number of single episodes tends to be kept constant. The central aspects of this kind of regulation have been examined biochemically in the preoptic-anterior hypothalamus, an area involved in the control of autonomic and sleep related processes. The results show that the accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) is impaired, in this region, during sleep deprivation and appears to return to the control levels, during the recovery, with a rate inversely related to the degree of the previous deprivation. Moreover, it has been observed that the systemic administration of DL-propranolol and LiCl reduces cAMP accumulation mainly in the preoptic-anterior hypothalamus; this condition is concomitant with a reduction in REM sleep occurrence.     

快速眼动睡眠产生的神经机制:蓝斑核神经元停止发放是一个必要的条件

两种类型的神经元参与了快速眼动（rapid eye movement,REM）睡眠的调节：快速眼动一发放（REM-ON）神经元和快速眼动-沉寂神经元（REM-OFF）。快速眼动-沉寂神经元属去甲肾上腺素能神经元,正如名字表示的那样——在快速眼动睡眠期间停止发放。已有研究表明,这些神经元放电活动的停止是导致快速眼动睡眠的前提条件,γ-氨基丁酸（γ-aminobutyric acid,GABA）可使它们停止发放。如果这嗤神经元不停止发放,脑中的去甲肾上腺素水平将升高,不出现快速眼动睡眠。剥夺快速眼动睡眠所引起的去甲肾上腺素增加,至少是快速眼动睡眠丧失引起Na^＋-K^＋ATP酶活性增加的原因,而这可能是导致快速眼动睡眠剥夺所引发的各种效应的主要因素。     

A world record in marathon tennis: sleep deprivation and performance

We studied the effects of marked sleep deprivation on the EEG patterns and performance of a physically fit man (age 26) on the occasion of the world record continuous marathon tennis play (147 hours, 20 minutes). Before and immediately after the marathon, the sleep patterns of the player were recorded in our laboratory. After playing for 40 and 80 hours and within 24 hours, the performance changes were evaluated each hour. Amounts of the different sleep stages during the first recovery night compared with those of the baseline indicate an increase of 56% for total sleep time, 54% for stages 1 and 2, 154% for stages 3 and 4 and 20% for REM sleep. During the second recovery night, only REM sleep showed an increase. Activity index showed a marked decrease after 80 hours of sleep deprivation compared with that after 40 hours and was dramatically worsened during nighttime. The number of faults and pauses was also increased after 80 hours, suggesting a clear performance deterioration. Our results confirmed the effects of sleep deprivation on the recovery and performance deterioration.     

Effects of β-endorphin on brain serotonin metabolism

Human β-endorphin (15 μg) administered intracisternally increased concentrations of serotonin (5HT) and its metabolite, 5-hydroxyindoleacetic. acid (5-HIAA), in brain stem and hypothalamus and decreased 5-HIAA concentrations in hippocampus. These data are compatible with the hypothesis that β-endorphin increases 5HT turnover in brain stem and hypothalamus and decreases 5HT turnover in hippocampus. β-endorphin increased in brain stem and hypothalamus and decreased in hippocampus the rate of pargyline-induced decline of 5-HIAA. β-endorphin decreased the rate of pargyline-induced accumulation of 5HT in all these brain regions. The probenecid-induced accumulation of 5-HIAA in brain stem was decreased by β-endorphin. These data are compatible with the hypothesis that β-endorphin increases release of 5HT from neurons in brain stem and hypothalamus and decreases release of 5HT from neurons in hippocampus. The data require further a hypothesis that β-endorphin either decreases 5HT reuptake in these three brain regions or increases 5-HIAA egress from brain.