Behavioral effects of the combined use of alcohol and energy drinks on alcohol hangover in an experimental mice model.

In last few years it has been a significant increase in the consumption of alcohol combined with energy drink. The aim of this work was to study the effect of this mixture in motor and affective behaviors during an alcohol hangover episode. Male Swiss mice received one of the following treatments: saline + sucrose; saline + energy drink; ethanol + sucrose; ethanol + energy drink. Ethanol dose was 3.8 g/kg BW (i.p.) and energy drink dose was 18 ml/kg BW (gavage) at ZT1 (8 am) (ZT: Zeitgeber time; ZT0: 7 am; lights on). The behavioral tests used were tight rope test to determine motor coordination; hanging wire test to study muscular strength; elevated plus maze and open field tests to evaluate anxiety like-behavior and locomotor activity. Tests were carried out at basal point that matched with lights onset and every 6 h up to 18 h after treatments. Hangover onset was established at ZT7 when blood alcohol concentration (BAC) was almost zero. Our results showed that the mixture of alcohol and energy drink altered significantly motor skills. Specifically, a significant decrease was observed in the performance of the animals in the tightrope and hanging wire tests in groups treated with the mixture of alcohol and energy drink. A significant impairment in the anxiety-like behavior was observed mainly at the beginning of alcohol hangover. These findings suggest that energy drink added to alcohol extends motor disabilities observed during an alcohol hangover episode in comparison with animals that received alcohol alone.

The effect of constant darkness and circadian resynchronization on the recovery of alcohol hangover.

Alcohol hangover (AH) is a particular state after binge-like drinking. AH begins when ethanol is absent in plasma and is characterized by a cluster of physical and psychological symptoms. Alcohol disrupts circadian patterns of behavioral and physiological parameters; however, the involvement of circadian clock on the recovery of AH was not explored. Our aim was to study the effect of continuous darkness and the possible involvement of the circadian clock in the recovery time of neuromuscular impairment and anxiety related-behavior due to AH. Male Swiss mice were habituated to 12:12 L:D or continuous darkness. Each group was injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Motor performance and anxiety phenotype were evaluated at a basal point (ZT0) and every 2 h up to 20 h after blood alcohol levels were close to zero (hangover onset). A third group was subjected to a phase advance during which a hangover episode was induced and behavioral tests were carried out for each group of treatment and resynchronization day. Constant darkness resulted to be in a faster recovery of both motor and anxiety impairments in AH compared with the recovery pattern observed under normal light-dark conditions. Mice suffering from a phase shift exhibited behavioral disruptions due to both AH and phase advance. Results indicated that a synchronized circadian clock is necessary for an adequate recovery of alcohol hangover symptoms.

Alterations in affective behavior during the time course of alcohol hangover.

Alcohol hangover is a temporary state described as the unpleasant next-day effects after binge-like drinking. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. Affective behavior is impaired during the acute phase of alcohol intoxication; however, no reports indicate if similar effects are observed during withdrawal. The aim of this work was to study the time-extension and possible fluctuations in affective behavior during a hangover episode. Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8g/kg BW) (hangover group). Anxiety, fear-related behavior and despair phenotype were evaluated at a basal point (ZT0) and every 2h up to 20h after blood alcohol levels were close to zero (hangover onset). Also, anhedonia signs and pain perception disabilities were studied. Mice exhibited an increase in anxiety-like behavior during 4h and 14h after hangover onset when evaluated by the elevated-plus maze and open field test respectively (p<0.05). Fear-related behavior was detected in hangover animals by the increase of freezing and decrease of line crossings and rearing frequency during 16h after hangover onset (p<0.001). Depression signs were found in hangover mice during 14h (p<0.05). Hangover mice showed a significant decrease in pain perception when tested by tail immersion test at the beginning of hangover (p<0.05). Our findings demonstrate a time-extension between 14 and 16h for hangover affective impairments. This study shows the long lasting effects of hangover over the phase of ethanol intoxication.

Alcohol hangover: type and time-extension of motor function impairments.

Alcohol hangover is defined as the unpleasant next-day state following an evening of excessive alcohol consumption. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. During hangover cognitive functions and subjective capacities are affected along with inefficiency, reduced productivity, absenteeism, driving impairments, poor academic achievement and reductions in motor coordination. The aim of this work was to study the type and length of motor and exploratory functions from the beginning to the end of the alcohol hangover. Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Motor performance, walking deficiency, motor strength, locomotion and exploratory activity were evaluated at a basal point (ZT0) and every 2 h up to 20 h after blood alcohol levels were close to zero (hangover onset). Motor performance was 80% decreased at the onset of hangover (p<0.001). Hangover mice exhibited a reduced motor performance during the next 16 h (p<0.01). Motor function was recovered 20 h after hangover onset. Hangover mice displayed walking deficiencies from the beginning to 16 h after hangover onset (p<0.05). Moreover, mice suffering from a hangover, exhibited a significant decrease in neuromuscular strength during 16 h (p<0.001). Averaged speed and total distance traveled in the open field test and the exploratory activity on T-maze and hole board tests were reduced during 16 h after hangover onset (p<0.05). Our findings demonstrate a time-extension between 16 to 20 h for hangover motor and exploratory impairments. As a whole, this study shows the long lasting effects of alcohol hangover.

Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover.

Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism.

Central cannabinoid 1 receptor antagonist administration prevents endotoxic hypotension affecting norepinephrine release in the preoptic anterior hypothalamic area.

It is widely assumed that LPS lowers arterial pressure during sepsis by stimulating release of TNF-alpha and other vasoactive mediators from macrophages. However, recent data from this and other laboratories have shown that LPS hypotension can be prevented by inhibiting afferent impulse flow in the vagus nerve, by blocking neuronal activity in the nucleus of the solitary tract, or by blocking alpha-adrenergic receptors in the preoptic area/anterior hypothalamic area (POA). These findings suggest that the inflammatory signal is conveyed from the periphery to the brain via the vagus nerve, and that endotoxic shock is mediated through a central mechanism that requires activation of POA neurons. In the present study, we tested whether central cannabinoid 1 (CB1) receptors participate in the control of arterial pressure during endotoxemia based on evidence that hypothalamic neurons express CB1 receptors and synthesize the endogenous CB anandamide. We found that intracerebroventricular administration of rimonabant, a CB1 receptor antagonist, inhibited the fall in arterial pressure evoked by LPS significantly in both conscious and anesthetized rats. Rimonabant attenuated both the immediate fall in arterial pressure evoked by LPS and the second, delayed hypotensive phase that leads to tissue ischemia and death. Rimonabant also prevented the associated LPS-induced rise in extracellular fluid norepinephrine concentrations in the POA. Furthermore, rimonabant attenuated the associated increase in plasma TNF-alpha concentrations characteristic of the late phase of endotoxic hypotension. These data indicate that central CB1 receptors may play an important role in the initiation of endotoxic hypotension.

Lipopolysaccharide-induced hypotension is mediated by a neural pathway involving the vagus nerve, the nucleus tractus solitarius and alpha-adrenergic receptors in the preoptic anterior hypothalamic area.

We recently reported that the preoptic anterior hypothalamic area (POA) mediates the hypotensive response evoked by lipopolysaccharide (LPS). In this study, we investigated how the inflammatory signal induced by LPS reaches the POA. Subdiaphragmatic vagotomy and abdominal perivagal lidocaine administration, or lidocaine injection into the nucleus tractus solitarius (NTS) prevented LPS hypotension. Microinjection of the alpha-adrenergic receptor antagonist phentolamine into the POA, blocked initiation of the hypotensive response and prevented the late decompensatory phase. These data suggest that LPS hypotension is mediated by the vagus nerve which conveys the signal to the NTS and, in turn, stimulates norepinephrine release within the POA.

Effects of prenatal stress on motor performance and anxiety behavior in Swiss mice.

Stressor presence during the last weeks of gestation has been associated with behavioral disorders in later life. In this study we support further research on the long term effects of prenatal stress on Swiss mice descendant's behavior. Prenatal stress procedure consisted on restraining the dams under bright light for 45 min, three times per day from the 15th day of pregnancy, until birth. After weaning, offspring's motor performance and spontaneous exploratory behavior were measured by the tight-rope and T-maze tests, respectively. We also evaluated anxiety behavior using elevated plus maze test. We found that maternal stress improves the performance of the animals in the tight rope test and that this effect was sex and age dependent: prenatal stressed males obtained the best scores during the first month of life, while in females the same was achieved at the second month. Spontaneous exploratory behavior analysis revealed that it was elevated in prenatal stressed males and that this effect persisted on time. However, we did not find significant differences on this behavioral response among both females groups. Finally, differences on anxiety behavior were found only in females: prenatally stressed animals showed a higher proportion of entries into the open arms of a plus maze (reduced anxiety) compared to the control group. Our results show that prenatal stress modifies the normal behavior of the progeny: prenatal stressed animals have a better performance in the carried out test. These notably results suggest the existence of an adaptive response to prenatal stress.

Melatonin effect on bone metabolism in rats treated with methylprednisolone.

The present study was undertaken to examine the effect of melatonin (25 microg/mL of drinking water, about 500 microg/day) on a 10-wk long treatment of male rats with methylprednisolone (5 mg/kg s.c., 5 days/wk). Bone densitometry and mechanical properties, calcemia, phosphatemia and serum bone alkaline phosphatase activity and C-telopeptide fragments of collagen type I (CTX) were measured. Both melatonin and methylprednisolone decreased significantly body weight (BW) and the combination of both treatments resulted in the lowest BW values found. Consequently, all results were analyzed with BW as a covariate. Densitometrically, methylprednisolone augmented bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) in the entire skeleton, BMC in cortical bone, and BMC and BMD in trabecular bone. Melatonin increased BMC and BA in whole skeleton and BMC and BMD in trabecular bone. For BMC and BA of whole skeleton, BMC of cortical bone, and BMC and BMD of trabecular bone, the combination of glucocorticoids and melatonin resulted in the highest values observed. Femoral weight of rats receiving methylprednisolone or melatonin increased significantly and both treatments summated to achieve the greatest effect. In femoral biomechanical testing, methylprednisolone augmented ultimate load and work to failure significantly. Rats receiving the combined treatment of methylprednisolone and melatonin showed the highest values of work to failure. The circulating levels of CTX, an index of bone resorption, decreased after methylprednisolone or melatonin, both treatments summating to achieve the lowest CTX values found. Serum calcium increased after methylprednisolone and serum phosphorus decreased after treatment with methylprednisolone or melatonin while serum bone alkaline phosphatase levels remained unchanged. The results are compatible with the view that low doses of methylprednisolone or melatonin decrease bone resorption and have a bone-protecting effect.

Melatonin treatment counteracts the hyperthermic effect of lipopolysaccharide injection in the Syrian hamster.

The present study examined the acute response in body temperature to lipopolysaccharide (LPS) injection to Syrian hamsters at two time intervals during the light-dark cycle. Its modification by melatonin (MT) administration in the drinking water was also assessed. Hamsters were intraperitoneally (i.p.) implanted with a transmitter to measure core body temperature. MT was administered from day 8 post-surgery until the end of experiment. On day 16 after surgery, LPS or saline was injected i.p. at the beginning of the light phase (ZT 0) or of the scotophase (ZT 14). At ZT 0, LPS increased core body temperature, an effect that persisted for at least 5h and that was blunted by MT administration. At ZT 14, the hyperthermic effect of LPS was absent. Rather, at ZT 14 the animals showed increases in core body temperature following saline or LPS during the first 2h after injection only, which were significantly less intense in LPS-treated animals. MT administration blunted this difference. Five days after injection, hamsters that had received LPS at ZT 0 showed an increase in the mesor of core body temperature rhythm as compared to saline. This effect was suppressed by MT administration. The results demonstrate that MT prevents body temperature increase after LPS at ZT 0.

Effect of interferon-gamma treatment on 24-hour variations in plasma ACTH, growth hormone, prolactin, luteinizing hormone and follicle-stimulating hormone of male rats.

OBJECTIVE: Interferon-gamma (IFN-gamma) is a cytokine produced by T helper cells on antigenic challenge that may affect the release of several pituitary hormones. However, in vitro or in vivo studies have yielded disparate results with stimulatory, inhibitory or absent effects of IFN on pituitary hormone release. One of the reasons for these discrepancies could be that hormone changes were commonly assessed at a single time point in the day-night cycle. In this study we measured the circadian pattern of plasma ACTH, growth hormone (GH), prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at 6 different time points within a 24-hour cycle in adult male Wistar rats. METHODS: Groups of 6-8 rats kept under light from 08:00 to 20:00 h daily received 5 daily injections intraperitoneally of human IFN-gamma (10(5) IU/kg body weight) or saline at 08:30 h. Plasma ACTH, GH, prolactin, LH and FSH levels were measured by a homologous specific double antibody RIA. RESULTS: A factorial ANOVA for main effects indicated a significant 43% increase of circulating prolactin in IFN-gamma-treated rats. Time of day changes were significant for the five hormones examined and these diurnal variations became altered by IFN-gamma administration, with a phase advance of ACTH peak, a suppression of the rest phase peak of GH, the appearance of a second peak of prolactin at an early phase of daily photoperiod, and the blunting of the 24-hour variations of plasma FSH. CONCLUSION: The data point out an effect of IFN-gamma on the mechanisms responsible for the circadian organization of pituitary hormone release.

Twenty-four-hour rhythms of mitogenic responses, lymphocyte subset populations and amino acid content in submaxillary lymph nodes of growing male rats subjected to calorie restriction.

Peripubertal male Wistar rats were submitted to a calorie restriction diet enriched in proteins and low in fat and carbohydrates for 4 weeks, and starting on day 35 of life. Mitogenic responses, lymphocyte subset populations, interferon (IFN)- gamma release and amino acid content were determined in submaxillary lymph nodes at six time intervals during the 24-h span. The diet employed completely arrested growth in growing rats. After caloric restriction, mean values of Con A response, lymph node T and CD4+ cell number and CD4+/CD8+ ratio augmented, whereas those of B cell number, IFN-gamma release and glutamine and glutamate concentration decreased. Calorie restriction modified 24-h rhythmicity of lymph node mitogenic responses to Con A and LPS, and of T, T-B, CD4+ and CD4+ -CD8+ lymph node cell subsets. It also changed the 24-h pattern of lymph node IFN-gamma release and glutamine, aspartate, glutamate and taurine lymph node content. Availability of nutrients presumably affects the mechanisms that modulate the circadian variation of immune responsiveness in growing rats.

Autonomic neural signals in bone: physiological implications for mandible and dental growth.

Signals derived from the autonomic nervous system exert potent effects on osteoclast and osteoblast function. A ubiquitous sympathetic and sensory innervation of all periosteal surfaces exists and its disruption affects bone remodeling. Several neuropeptides, neurohormones and neurotransmitters and their receptors are detectable in bone. Bone mineral content decreased in sympathetically denervated mandibular bone. When a mechanical stress was superimposed on mandibular bone by cutting out the lower incisors, an increase in bone density ensued providing the sympathetic innervation was intact. A lower eruption rate of sympathetically denervated incisors at the impeded eruption side, and a higher eruption rate of denervated incisors at the unimpeded side were also observed. A normal sympathetic neural activity appears to be a pre-requisite for maintaining a minimal normal unimpeded incisor eruption and for keeping the unimpeded eruption to attain abnormally high velocities under conditions of stimulated incisor growth. These and other results suggest that the sympathetic nervous system plays an important role in mandibular bone metabolism.

Effect of unilateral superior cervical ganglionectomy on mandibular bone in rats.

OBJECTIVE: To assess the effect of local sympathectomy on mandibular bone during tooth eruption in rats. METHODS: The effect of a unilateral superior cervical ganglionectomy (Gx) on morphometry of ipsi- and contralateral mandible and volumetric bone density (as assessed by peripheral computed tomography) was examined 30 days after surgery. RESULTS: Only a few mandibular morphometric parameters decreased significantly after denervation in rats subjected to a unilateral Gx and a contralateral sham-operation. Mandibular volumetric bone density decreased significantly after sympathetic denervation. In a second experiment, carried out under conditions of unilateral unimpeded eruption of incisors performed ipsilaterally or contralaterally to a unilateral Gx, a significant interaction "denervation x type of eruption" was found for most morphometric parameters. Further analysis indicated higher morphometric indexes in denervated mandibles than in the innervated ones under impeded incisor eruption conditions, and lower morphometric indexes in denervated mandibles than in the innervated ones under unimpeded incisor eruption conditions. Unimpeded eruption augmented total volumetric bone density providing the innervation was intact and caused opposite effects on cortical volumetric bone density in the presence of innervation (increase) or absence of innervation (decrease). Trabecular volumetric bone density decreased significantly after sympathetic denervation. CONCLUSION: The results support a role of the sympathetic nervous system in the regulation of bone remodeling.

Cerebroventricular administration of interferon-gamma modifies locomotor activity in the golden hamster.

The present study was undertaken to examine whether the intracerebroventricular (i.c.v.) administration of interferon (IFN)-gamma could modify 24-hour wheel running locomotor activity in the golden hamster. Hamsters implanted with a cannula in the third ventricle received a single i.c.v. injection of 1 microl of murine recombinant IFN-gamma (40 IU/microl) or its vehicle (saline) at ZT 6 or ZT 18 (with ZT 12 defined arbitrarily as the time of lights off) and their activities were monitored during 24 h. The i.c.v. administration of IFN-gamma at ZT 6 produced a significant phase advance in acrophase of rhythm, an effect not seen at ZT 18. Also, IFN-gamma depressed mesor value significantly, the effect was seen at both times. These results clearly showed that the circadian clock could be modified by IFN-gamma microinjections. One explanation could be the presence of IFN-gamma receptor in the rat suprachiasmatic nucleus, supporting a direct effect on the central oscillator. However, another hypothesis could not be ruled out.

Melatonin effects on bone: experimental facts and clinical perspectives.

Bone formation proceeds through a remodeling process that runs continuously, involving the resorption of old bone by osteoclasts, and the subsequent formation of new bone by osteoblasts. This is controlled by growth factors and cytokines produced in bone marrow microenvironment and by the action of systemic hormones, like parathyroid hormone, estradiol or growth hormone (GH). One candidate for hormonal modulation of osteoblast and osteoclast formation is melatonin. Because circulating melatonin declines with age, its possible involvement in post-menopausal and senescence osteoporosis is considered. This review article discusses early studies on melatonin-bone relationships and recent data that suggest a direct effect of melatonin on bone. Melatonin could act as an autacoid in bone cells as it is present in high quantities in bone marrow, where precursors of bone cells are located. Melatonin dose-dependently augmented proteins that are incorporated into the bone matrix, like procollagen type I c-peptide. Osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts is also augmented by melatonin in vitro. Another possible target cell for melatonin is the osteoclast, which degrades bone partly by generating free radicals. Melatonin through its free radical scavenger and antioxidant properties may impair osteoclast activity and bone resorption. At least in one study melatonin was both inhibitory to osteoclastic and osteoblastic cells. Therefore, the documented bone-protecting effect of melatonin in ovariectomized rats can depend in part on the free radical scavenging properties of melatonin. Additionally, melatonin may impair development of osteopenia associated with senescence by improving non-rapid eye movement sleep and restoring GH secretion. Whether melatonin can be used as a novel mode of therapy for augmenting bone mass in diseases deserves to be studied.

A multifactorial approach employing melatonin to accelerate resynchronization of sleep-wake cycle after a 12 time-zone westerly transmeridian flight in elite soccer athletes.

Rapid transmeridian translocation through multiple time zones has a negative impact on athletic performance. The aim of the present study was to test the timely use of three factors (melatonin treatment, exposure to light, physical exercise) to hasten the resynchronization of a group of elite sports competitors and their coaches to a westerly transmeridian flight comprising of 12 time-zones. Twenty-two male subjects were included in the study. They were professional soccer players and their coaches who travelled to Tokyo to play the final game of the Intercontinental Coup. The day prior to departure, urine was collected from each subject from 18:00 to 06:00 hrs to measure the melatonin metabolite 6-sulphatoxymelatonin. Participants were asked to complete sleep log diaries from day 0 (preflight) to the day before returning to Buenos Aires (day 8). All subjects received 3 mg of melatonin p.o. daily at expected bedtime at Tokyo immediately after leaving Buenos Aires. Upon arrival at Tokyo the subjects performed a daily physical exercise routine outdoors at two restricted times of the day (from 08:00 to 11:00 hrs in the morning and from 13:00 to 16:00 hrs in the afternoon). Exposure to sunlight or physical exercise at other times of the day was avoided. Except for the number of awakenings (which increased on days 1 and 3) and sleep latency (which decreased on days 2, 6 and 8), there was an absence of significant changes in subjective sleep parameters as compared with preflight assessment. Sleep quality and morning alertness at Tokyo correlated significantly with preflight 6-sulphatoxymelatonin excretion. Mean resynchronization rate of sleep-wake cycle to the 12 hr-time shift was 2.13 +/- 0.88 days, significantly different from the minimal resynchronization rate of 6 days expected after a 12-time-zones flight. The results indicate that the combination of melatonin treatment, an appropriate environmental light schedule and timely applied physical exercise can be useful to help elite athletes to overcome the consequences of jet lag.

Effect of melatonin on changes in locomotor activity rhythm of Syrian hamsters injected with beta amyloid peptide 25-35 in the suprachiasmatic nuclei.

1. Alzheimer's disease is associated with circadian rhythm disturbances, probably because of beta amyloid-induced neuronal damage of hypothalamic suprachiasmatic nuclei (SCN). 2. Since there is no published study on the circadian consequences of injecting beta amyloid peptide in experimental animals, one objective of the present study was to examine circadian locomotor activity in Syrian hamsters injected with beta amyloid peptide 25-35 into both SCN. 3. Because one of the proposed therapies for circadian alterations in dementia is the administration of melatonin, a chronobiotic agent with antioxidant properties, the preventive effect of melatonin on the circadian changes produced by beta amyloid microinjection into SCN was also assessed. 4. Wheel running activity was recorded by using the Dataquest III system in male golden hamsters kept under 14:10 light-dark photoperiods. Animals received microinjections of beta amyloid peptide 25-35 (100 microM solution, 1 microL) or saline in each SCN. Only those animals with neuronal lesions larger than 10% of SCN after beta amyloid injection were considered for further analysis. 5. To assess the effect of melatonin on beta-amyloid peptide activity, melatonin was given in the drinking water (25 microg/mL) starting 15 days in advance to the microinjection of beta amyloid peptide into SCN. 6. Beta amyloid-treated hamsters exhibited a significant phase advance of onset of running activity of about 22 min as compared to saline-injected animals. They also showed a significantly greater variability in onset time of wheel running activity, mainly evident from 6 to 15 days of treatment. 7. Melatonin administration in the drinking water prevented the phase advance of onset time and the increased variability of onset time brought about by beta amyloid peptide. 8. The results support the existence of a neuroprotective effect of melatonin on beta amyloid-induced circadian changes in hamsters.