Effects of acute handling stress on cerebral monoaminergic neurotransmitters in juvenile Senegalese sole Solea senegalensis.

Juvenile Senegalese sole Solea senegalensis were subjected for short periods to two different types of handling-related stress: air exposure stress and net handling stress. The S. senegalensis were sacrificed 2 and 24 h after the stress events and the levels of serotonin (5-HT), noradrenaline (NA), dopamine (DA) and their respective major metabolites, 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC), were measured in three brain regions (telencephalon, hypothalamus and optic tectum) and compared with those in control, non-stressed S. senegalensis. Neither type of stress caused any significant alteration of serotoninergic activity (5-HIAA:5-HT ratio) or NA levels. Dopaminergic activity (DOPAC:DA ratio) was lower in stressed fish in all of the brain regions studied. For both air exposure stress and net handling stress, DA levels were significantly higher (P < 0.05) than in the control S. senegalensis. In addition, the higher DA levels after net handling stress were always significantly higher (P < 0.05) than those observed after acute air exposure stress, except in the telencephalon after 24 h. The significantly lower DOPAC:DA ratio (P < 0.05) in all of the brain regions studied was only observed in response to net handling stress.

Brain glycogen supercompensation after different conditions of induced hypoglycemia and sustained swimming in rainbow trout (Oncorhynchus mykiss).

Brain glycogen is depleted when used as an emergency energy substrate. In mammals, brain glycogen levels rebound to higher than normal levels after a hypoglycemic episode and a few hours after refeeding or administration of glucose. This phenomenon is called glycogen supercompensation. However, this mechanism has not been investigated in lower vertebrates. The aim of this study was therefore to determine whether brain glycogen supercompensation occurs in the rainbow trout brain. For this purpose, short-term brain glucose and glycogen contents were determined in rainbow trout after being subjected to the following experimental conditions: i) a 5-day or 10-day fasting period and refeeding; ii) a single injection of insulin (4 mg kg(-1)) and refeeding; and iii) sustained swimming and injection of glucose (500 mg kg(-1)). Food deprivation during the fasting periods and insulin administration both induced a decrease in glucose and glycogen levels in the brain. However, only refeeding after 10 days of fasting significantly increased the brain glycogen content above control levels, in a clear short-term supercompensation response. Unlike in mammals, prolonged exercise did not alter brain glucose or glycogen levels. Furthermore, brain glycogen supercompensation was not observed after glucose administration in fish undergoing sustained swimming. To our knowledge, this is the first study providing direct experimental evidence for the existence of a short-term glycogen supercompensation response in a teleost brain, although the response was only detectable after prolonged fasting.

Effects of acute exposure to exogenous ammonia on cerebral monoaminergic neurotransmitters in juvenile Solea senegalensis.

The present study explored the potential role of brain catecholaminergic and serotoninergic systems as neuronal targets for the toxicological effects of acute ammonia exposure (0.28 mg l(-1) of un-ionized ammonia for 12 and 24 h) in juvenile sole (Solea senegalensis). In addition, plasma cortisol levels were measured. The results showed significant increases in their concentrations that were similar after 12 and 24 h of exposure. These data indicate that acute exposure (12 and 24 h) to ammonia initiates a typical stress response in the Senegalese sole, with stimulation of the hypothalamus-pituitary-interrenal axis. The concentrations of dopamine (DA), serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (NA), and their metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-3-indoleacetic acid (5HIAA), were measured in the hypothalamus, telencephalon and optic tectum. The main changes induced by acute exposure to ammonia were decreases in the concentrations of 5-HT and DA, which were significant in most of the brain regions studied. The ratios of 5-HIAA/5-HT and DOPAC/DA increased in all regions and at all times studied, although in the case of the DOPAC/DA ratio, the increases were only significant in the hypothalamus (24 h exposure) and in the optic tectum (12 and 24 h exposure). These changes indicated that exposure to ammonia elicited time-dependent increases in serotoninergic and dopaminergic activity in the hypothalamus, telencephalon and optic tectum.

Atomistic mesh generation for the simulation of nanoscale metal-oxide-semiconductor field-effect transistors.

We present a methodology for the finite-element discretization of nanoscaled semiconductor devices with atomic resolution. The meshing strategy is based on the use of patterns to decompose the unit cell of the underlying crystallographic structures producing unstructured tetrahedral meshes. The unit cells of the bulk semiconductors and, more importantly, of the interfaces between the substrate and the gate dielectric have been extracted from classical molecular dynamics and density functional theory simulations. A Monte Carlo approach has been then used to place the dopants in nodes of the crystal, replacing silicon atoms. The thus created "atomistic" meshes are used to simulate an ensemble of microscopically different double-gate Si metal-oxide-semiconductor field-effect transistors and the transition region at the Si/SiO_{2} interface. In addition, a methodology to approximate amorphous dielectrics is also presented.

Effects of reserpine and p-chloroamphetamine on 5-HT metabolism and release in the cerebral ganglia of Inachis io (Lepidoptera).

There have been few pharmacological studies of serotonergic system dynamics in insects. A more precise knowledge of the response of serotonergic neurons to drugs will contribute to understanding of the role of this neurotransmitter in insect behaviour. The present work was carried out to study several aspects of serotonin (5-HT) metabolism and release in an insect, the butterfly Inachis io. The effects of a single intra-abdominal injection of reserpine (30 pg/insect) or p-chloroamphetamine (50 microg/insect) on cerebral ganglia 5-HT metabolism and release were studied. After reserpine injection a depletion of 5-HT stores concomitant with an increase in N-acetylserotonin levels was observed, but not significant alteration of extraneuronal 5-HT release was observed. Administration of p-chloroamphetamine (PCA) induced extraneuronal 5-HT release, together with inhibition of its reuptake. Finally, a single injection of p-chloroamphetamine in reserpine-treated insects was able to induce new release of 5-HT. Reserpine interferes with the vesicular storage of 5-HT, but does not affect the process of neuronal release, while PCA induces the synaptic release of 5-HT and inhibits its reuptake. These effects are similar to those observed in mammals.

Effects of reserpine and p-chloroamphetamine on 5-HT metabolism and release in the cerebral ganglia of Inachis io (Lepidoptera)

There have been few pharmacological studies of serotonergic system dynamics ininsects. A more precise knowledge of the response of serotonergic neurons to drugswill contribute to understanding of the role of this neurotransmitter in insect behaviour.The present work was carried out to study several aspects of serotonin (5-HT)metabolism and release in an insect, the butterfly Inachis io. The effects of a singleintra-abdominal injection of reserpine (30 ìg/insect) or p-chloroamphetamine (50ìg/insect) on cerebral ganglia 5-HT metabolism and release were studied. Afterreserpine injection a depletion of 5-HT stores concomitant with an increase in Nacetylserotoninlevels was observed, but not significant alteration of extraneuronal 5-HT release was observed. Administration of p-chloroamphetamine (PCA) inducedextraneuronal 5-HT release, together with inhibition of its reuptake. Finally, a singleinjection of p-chloroamphetamine in reserpine-treated insects was able to induce newrelease of 5-HT. Reserpine interferes with the vesicular storage of 5-HT, but does notaffect the process of neuronal release, while PCA induces the synaptic release of 5-HT and inhibits its reuptake. These effects are similar to those observed in mammals (AU)

No disponible

Effects of reserpine and p-chloroamphetamine on5-HT metabolism and release in the cerebralganglia of Inachis io (Lepidoptera)

There have been few pharmacological studies of serotonergic system dynamics ininsects. A more precise knowledge of the response of serotonergic neurons to drugswill contribute to understanding of the role of this neurotransmitter in insect behaviour.The present work was carried out to study several aspects of serotonin (5-HT)metabolism and release in an insect, the butterfly Inachis io. The effects of a singleintra-abdominal injection of reserpine (30 ìg/insect) or p-chloroamphetamine (50ìg/insect) on cerebral ganglia 5-HT metabolism and release were studied. Afterreserpine injection a depletion of 5-HT stores concomitant with an increase in Nacetylserotoninlevels was observed, but not significant alteration of extraneuronal 5-HT release was observed. Administration of p-chloroamphetamine (PCA) inducedextraneuronal 5-HT release, together with inhibition of its reuptake. Finally, a singleinjection of p-chloroamphetamine in reserpine-treated insects was able to induce newrelease of 5-HT. Reserpine interferes with the vesicular storage of 5-HT, but does notaffect the process of neuronal release, while PCA induces the synaptic release of 5-HT and inhibits its reuptake. These effects are similar to those observed in mammals (AU)

No diponible

Peripheral serotonin dynamics in the rainbow trout (Oncorhynchus mykiss).

Serotonin (5-hydroxytryptamine, 5-HT) occurs in a wide range of tissues throughout the body of the rainbow trout. Results reported here indicate that the main peripheral sources of serotonin are the intestinal tract and the gill epithelium (levels above 1500 ng/g). The high intestinal serotonin concentration is mostly due to serotoninergic nerve fibres, which are present at high density in the intestinal wall. Only about 2% of serotonin is associated with mucosal enterochromaffin cells. In the remaining tissues studied serotonin concentration was below 160 ng/g: the highest concentrations were seen in the anterior and posterior kidneys, followed by the liver, heart, and spleen. 5-Hydroxyindolacetic acid (5-HIAA) levels, except in plasma, were generally lower than serotonin levels, and were below our detection limits in heart, spleen and posterior kidney. Acute d-fenfluramine treatment (5 or 15 mg/kg i.p.) significantly increased 5-HIAA/5-HT ratio in the anterior intestine, pyloric caeca and plasma. Serotonin released from intestinal serotoninergic fibres in response to d-fenfluramine treatment is metabolized locally, and only a small part reaches the blood, from where it can be taken up and metabolized by other peripheral tissues, such as the liver and gill epithelium. The non-metabolized serotonin pool in the blood appears to be located extracellularly, not intracellularly as in mammals. In view of these findings, we present an overview of peripheral serotonin dynamics in rainbow trout.

Effects of neuropeptide Y on food intake and brain biogenic amines in the rainbow trout (Oncorhynchus mykiss).

Neuropeptide Y (NPY) is one of the most potent stimulants of food intake in mammals, but very little is known about NPY actions in fish. The present study investigated the role of NPY in food intake in the rainbow trout (Oncorhynchus mykiss). Food intake was monitored at different times after intracerebroventricular administration of porcine NPY (4 or 8 microg). Both doses significantly increased food intake at 2 and 3 h, and this effect was dose-dependent. However, 50 h after administration of NPY, food intake was significantly lower than in control fish, and cumulative food intake had returned to levels similar to those seen in the control group. The NPY antagonist (D-Tyr27,36, D-Thr32)-NPY (10 microg) inhibited food intake 2 h after icv administration, but did not block the orexigenic effect of NPY when administered jointly with 4 microg NPY. To identify the NPY receptor subtypes involved in the effects of NPY on food intake, we studied the effects of the Y1 receptor agonist (Leu31, Pro34)-NPY (4 microg), the Y2 receptor agonist NPY(3-36) (4 microg), and the highly specific Y5 receptor agonist (cPP(1-7), NPY19-23, Ala31, Aib32, Gln34)-hPP (4 microg). Short-term (2 h) food intake was moderately stimulated by the Y1 agonist, more strongly stimulated by the Y2 agonist, and unaffected by the Y5 agonist. We found that administration of NPY (8 microg icv) had no effect on aminergic systems in several brain regions 2 and 50 h after NPY administration. These results indicate that NPY stimulates feeding in the rainbow trout, and suggest that this effect is cooperatively mediated by Y2- and Y1-like NPY receptors, not by Y5-like receptors.

Brain glucose and insulin: effects on food intake and brain biogenic amines of rainbow trout.

The effects of central (intracerebroventricular, 9 microg fish(-1)) and peripheral (intraperitoneal, 4 mg kg(-1)) administration of bovine insulin, as well as the effect of hyperglycemia (oral administration of 1 g glucose fish(-1)) and brain glucodeprivation (intracerebroventricular administration of 2-deoxy-D-glucose) on food intake and levels of brain (telencephalon, preoptic area, and hypothalamus) biogenic amines (serotonin, dopamine, noradrenaline and their metabolites 5-hydroxyindoleacetic acid, and dihydroxyphenylacetic acid) were assessed on rainbow trout ( Oncorhynchus mykiss). Treatment with insulin inhibited food intake after 26 or 52 h of administration, central or peripheral, respectively. This effect was still apparent after 74 h of central treatment. When assessing changes in the levels of biogenic amines after 26 h of central insulin administration, there was a significant increase in the levels of 5-hydroxyindoleacetic acid, and in the ratio of dihydroxyphenylacetic acid/dopamine of insulin-treated fish, in telencephalon and hypothalamus, respectively. These results suggest that peripherally administered insulin is involved in a feedback regulatory loop with food intake and body weight. Moreover, at least part of the effects of insulin could be mediated by hypothalamic dopaminergic activity. The strong hyperglycemia induced by oral administration of glucose did not induce significant changes either on food intake (control versus treated), or in brain levels of biogenic amines. The intracerebroventricular administration of 2-deoxy-D-glucose induced an increase in food intake without altering plasma glucose levels, suggesting that fish brain possesses a control system for detecting hypoglycemia in plasma and therefore keep brain glucose levels high enough for brain function.

Effects of acute 17alpha-methyltestosterone, acute 17beta-estradiol, and chronic 17alpha-methyltestosterone on dopamine, norepinephrine and serotonin levels in the pituitary, hypothalamus and telencephalon of rainbow trout (Oncorhynchus mykiss).

This study investigated: (a) the effects of acute 17alpha-methyltestosterone (MT) or 17beta-estradiol (E(2)) administration on norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4, dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) contents in the hypothalamus, telencephalon and pituitary of previtellogenic female rainbow trout Oncorhynchus mykiss, and (b) the effects of chronic MT administration on the levels of these neurotransmitters in these brain regions in immature male rainbow trout. The acute administration of MT induced a significant decrease in pituitary levels of DOPAC as well as in the DOPAC/DA ratio. On the other hand, the acute administration of E(2) induced an increase in pituitary 5-HT levels as well as a decrease in the 5-HIAA/5-HT ratio. In a second experiment, 20 mg MT per kilogram body weight was implanted for 10, 20 or 40 days into sexually immature male rainbow trout. Implanted rainbow trout showed increased testosterone and decreased E(2) levels. In the pituitary, MT induced long-term decreases in NE, DA, DOPAC and 5-HT levels, as well as in the DOPAC/DA ratio. Hypothalamic and telencephalic DA, NE and 5-HT levels were not affected by MT implantation. However, 5-HIAA levels and the 5-HIAA/5-HT ratio were reduced by MT implantation in both brain regions. These results show that chronic treatment with MT exerts both long-term and region-specific effects on NE, DA, and 5-HT contents and metabolism, and thus that this androgen could inhibit pituitary catecholamine and 5-HT synthesis. A possible role for testosterone in the control of pituitary dopaminergic activity and gonadotropin II release is also discussed.

Brain serotonin and the control of food intake in rainbow trout (Oncorhynchus mykiss): effects of changes in plasma glucose levels.

The levels of 5-hydroxytryptamine and its main metabolite 5-hydroxyindoleacetic acid were assessed in two brain regions, hypothalamus and telencephalon, of rainbow trout (Oncorhynchus mykiss) submitted to increases or decreases in plasma glucose levels through different experimental approaches. Thus, intraperitoneal glucose treatment (500 mg kg(-1)) increased 5-hydroxytryptamine telencephalic levels. Long-term food deprivation up to 3 weeks significantly increased hypothalamic (2 weeks and 3 weeks) and telencephalic (1 week, 2 weeks, and 3 weeks) levels of 5-hydroxyindoleacetic acid, whereas the ratio 5-hydroxyindoleacetic acid/5-hydroxytryptamine significantly increased throughout the food-deprivation period assessed. Intraperitoneal treatment with bovine insulin (4 mg kg(-1)) decreased the 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio in hypothalamus after 1 h. Intraperitoneal administration of fenfluramine (3 mg kg(-1)) caused a depression in food intake coincident with a significant decrease of the hypothalamic 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio. These data are discussed in the context of the involvement of serotonergic system in the control of food intake in rainbow trout.

Effects of melatonin on dopamine metabolism in the hypothalamus and the pituitary of the rainbow trout, Oncorhynchus mykiss.

The present paper discusses the effect of a single melatonin treatment (0.5 mg/kg, i.p.) on the dopaminergic metabolism in the hypothalamus and pituitary of the rainbow trout. The effects of exogenous melatonin on dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents were compared with the variations in the content of these catecholamines associated to the natural increase in the endogenous melatonin from daytime (3 hr before lights off) to nighttime (3 hr after lights off). Animals treated with melatonin showed a rapid (maximal values at 30 min post-injection) and relatively sustained rise in plasma melatonin levels, which reached supraphysiological ranges. The increase in circulating melatonin was accompanied by a reduction in the amount of DOPAC in both the hypothalamus (30, 60, and 120 min after i.p. melatonin) and the pituitary (120 min after i.p. melatonin) as well as in the pituitary DOPAC/DA ratio (60 and 120 min after i.p. melatonin). Similarly, the increase in circulating melatonin levels from the daytime to nighttime was associated with decreases in the contents of DOPAC in both the hypothalamus and pituitary and in the DOPAC/DA ratio in the pituitary. These data suggest that the inhibition of the hypothalamic-pituitary dopaminergic metabolism may be a specific mechanism of melatonin action in the trout brain that might operate following changes in the secretion of the hormone from the pineal gland.

Pharmacological modification of the serotonergic transmitter system and beta-N-acetylhexosaminidase activity in rats.

The enzyme activity and activation energy of plasma beta-N-acetylhexosaminidase (Hex) was determined in rats whose serotonergic system had been pharmacologically altered. In the group of animals treated with 5-hydroxytryptophan, in the different dissected brain regions (brain stem, cortex and hippocampus) significantly higher levels of serotonin and 5-hydroxyindolacetic acid were found, and significantly lower in the group treated with p-chlorophenylalanine, than in the control group. In the total number of animals studied (n = 21), a statistically significant correlation was found between the plasma concentration of 5-hydroxyindolacetic acid and the levels of this metabolite in the different brain regions (p < 0.001). No significant differences were found for the activity of Hex in the plasma, or for its activation energy, which is a marker of its isoenzyme composition, among the three groups of animals. The results obtained using our experimental model in rats do not confirm the hypothesis of other authors who suggest that the Hex responds secondary to increases or decreases of serotonin turnover, and could be a biological test to monitor the serotonin status in psychiatric patients.

Uptake of 3-O-methyl-D-[U-14C]glucose into brain of rainbow trout: possible effects of melatonin.

The influx of glucose into the brain and plasma glucose disappearance were estimated in rainbow trout (Oncorhynchus mykiss) intravenously injected (1 ml x kg(-1) body weight) with a single dose (15 microCi x kg(-1) body weight) of 3-O-methyl-D-[U-14C]glucose ([U-14C]-3-OMG) at different times (2-160 min), and after intravenous injection at 15 min of increased doses (10-60 microCi x kg(-1) body weight) of [U-14C]-3-OMG. Brain and plasma radiotracer concentrations were measured, and several kinetic parameters were calculated. The apparent brain glucose influx showed a maximum after 15-20 min of injection then decreased to a plateau after 80 min. Brain distribution space of 3-OMG increased from 2 min to 20 min reaching equilibrium from that time onwards at a value of 0.14 ml x g(-1). The unidirectional clearance of glucose from blood to brain (k1) and the fractional clearance of glucose from brain to blood (k2) were estimated to be 0.093 m x min(-1) x g(-1), and 0.867 min(-1), respectively. A linear increase was observed in brain and plasma radiotracer concentrations when increased doses of [U-(14)C]3-OMG were used. All these findings support a facilitative transport of glucose through the blood-brain barrier of rainbow trout with characteristics similar to those observed in mammals. The injection of different doses of melatonin (0.25-1.0 mg x kg(-1)) significantly increased brain glucose influx suggesting a possible role for melatonin in the regulation of glucose transport into the brain.

Acute effects of L-tryptophan on tryptophan hydroxylation rate in brain regions (hypothalamus and medulla) of rainbow trout (Oncorhynchus mykiss).

Levels of 5-hydroxytryptophan (5-HTP) in brain regions (hypopthalamus and medulla) of rainbow trout were analysed by HPLC-EC 0, 10, 30, and 40 min after intraperitoneal administration of different doses of L-tryptophan (Trp) (0, 12.5, and 25 mg. kg(-1) body weight) in fish treated with 3-hydroxybenzylhydrazine (NSD1015; 75 mg. kg(-1)). The results show that, in control fish, 5-HTP levels in hypothalamus (58.03 +/- 6.36 pg. mg(-1) brain tissue) were significantly higher than those observed in medulla (28.04 +/- 4.32 pg. mg(-1) brain tissue). Basal tryptophan hydroxylation rates (after 0 mg. kg(-1) Trp administration) were 0.42 +/- 0.07 pg 5-HTP. mg(-1). min(-1), and 0.63 +/- 0.24 pg 5HTP. mg(-1). min(-1), for hypothalamus and medulla respectively. On the other hand, the results demonstrate that L-tryptophan administration induced significant increases in the rate of tryptophan hydroxylation, both in hypothalamus and medulla. These findings indicate that, in a way similar to that observed in mammals, brain tryptophan hydroxylase is unsaturated by its substrate (tryptophan) under normal physiological conditions. J. Exp. Zool. 286:131-135, 2000.

Changes in the pituitary metabolism of monoamines (dopamine, norepinephrine, and serotonin) in female and male rainbow trout (Oncorhynchus mykiss) during gonadal recrudescence.

The dynamics of the levels and metabolism of dopamine, norepinephrine, and serotonin were studied in pituitaries of male and female rainbow trout at different stages of gonadal development. In female rainbow trout, the turnover of dopamine (calculated using the inhibitor of tyrosine hydroxylase alpha-methyl-p-tyrosine methyl-ester HCl), serotonin metabolism, and norepinephrine levels decreased in the advanced stage of exogenous vitellogenesis with respect to the initial stage. However, data obtained in males did not show changes in either serotonergic or noradrenergic metabolism during the last stages of gonadal development. However, an increase of dopaminergic turnover was noticed in the male fish at the end of spermiation. Finally, pituitary dopaminergic activity was significantly higher in immature (prepubescent stage) than in adult fish.

Selective changes in the contents of noradrenaline, dopamine and serotonin in rat brain areas during aging.

This study examines the age-associated changes in noradrenaline (NA), dopamine (DA), 3,4-dihydroxyphenyl-acetic acid (DOPAC), serotonin (5-HT) and 5-hydroxy-3-indoleacetic acid (5-HIAA) in different brain areas of rats. DA and DOPAC concentrations in striatum increased at third month of age, remaining without significant variations until 12th month of age, and decreasing in 24-month-old rats. DA concentration dropped in hippocampus, amygdala and brainstem of 24-month-old-rats, whereas DOPAC levels decreased only in hippocampus. These changes suggest an age-dependent deficit of the dopaminergic system, presumably related to a reduced number/activity of DA nigrostriatal and mesolimbic neurons. An age-induced decline in NA content was found in the pons-medulla, the area containing NA neuronal bodies. Concentrations of 5-HT were reduced with aging in frontal cortex, showing a tendency to decrease in all brain areas examined. The increased 5-HIAA/5-HT ratio found in frontal cortex, amygdala and striatum suggests an age-related decreased synthesis and an accelerated 5-HT metabolism. The 5-HIAA content decreased in brainstem of the oldest rats. These findings point to a selective impairment of nigrostriatal and mesolimbic DA in aging rats, whereas reductions in NA were restricted to cell bodies region and 5-HT showed changes of different extent in areas of terminals and neuronal cell bodies.

Changes with age in daytime and nighttime contents of melatonin, indoleamines, and catecholamines in the pineal gland: a comparative study in rat and Syrian hamster.

Previous studies in rodents showed a severe deterioration of pineal physiology with aging. The present study investigated the age-related changes in the content of monoamines and metabolites in rat and Syrian hamster pineal gland. In addition to melatonin, the levels of 5-hydroxytryptophan (5HTP), serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), N-acetylserotonin (N-Ac-SHT), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and noradrenaline (NA) were measured by HPLC. Pronounced reductions were found in 5HT and 5HIAA contents during daytime in rats of 24 months, which had not been observed in animals of 12 months. In addition, nighttime pineal 5HIAA, N-Ac-5HT, and melatonin contents were decreased in the old rats, although a significant day:night variation persisted. Also a diurnal fluctuation in NA, DA, and DOPAC contents was present in young and middle-aged rats but not for NA and DOPAC in the oldest rats due to a decrease in the nighttime levels. Pineal DA levels were also reduced in 24-month-old rats during the night, although a marked day:night change was still found. In the Syrian hamster pineal, significant reductions in daytime 5HT and 5HIAA were found respectively at 12 and 18 months, while nighttime levels of these compounds were decreased from 18 months. The nocturnal content of N-Ac-5HT dropped gradually from 12 months, and melatonin was reduced by 74% and 86% in hamsters of 18 and 24 months, respectively. In all these compounds, a significant day:night variation was observed irrespective of age. However, neither a day:night variation nor an effect of aging was found in terms of pineal NA content. In contrast, pineal DA and DOPAC levels displayed a diurnal variation in hamsters of 1.5 and 6 months, but not in animals of 12 and 18 months due a reduced nighttime content. These data suggest that the decline of pineal melatonin with age is a consequence of a deficit in the pathway of serotonin utilization. This probably is explained by a reduced N-acetyltransferase activity, which may be linked to impaired pineal catecholaminergic neurotransmission.