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.     

Effect of Melatonin Treatment on 24-hour Variations in Hypothalamic Serotonin and Dopamine Turnover During the Preclinical Phase of Freund's Adjuvant Arthritis in Rats

The effect of melatonin treatment on time-of-day variations in hypothalamic serotonin (5-HT) and dopamine (DA) turnover was studied in rats treated with Freund's complete adjuvant (FCA). Animals received s.c. injections of 30 æg of melatonin or vehicle 1 h before lights off for 11 days. On day 10 of treatment, FCA or its vehicle was s.c. injected, and 2 days later, the rats were killed at 6 different time intervals throughout a 24-hour cycle. Hypothalamic 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA), DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured by HPLC. 5-HT and DA turnover were estimated from the 5-HIAA/5-HT and DOPAC/DA ratios, respectively. In the anterior hypothalamus, time-of-day variation in 5-HT turnover was suppressed by FCA, an effect counteracted by melatonin treatment. Melatonin also prevented FCA effect on medial hypothalamic 5-HT turnover, while in the posterior hypothalamus, similar daily variations of 5-HT turnover were found in all experimental groups. As far as DA turnover, FCA or melatonin administration suppressed its daily variations in the anterior hypothalamus. Time-of-day variations in medial hypothalamic DA turnover were similar in all groups while only rats treated with melatonin and FCA or its vehicle exhibited significant daily changes of DA turnover in the posterior hypothalamus. Results indicate that melatonin treatment affects partly the 24-hour pattern of variation of hypothalamic 5-HT and DA turnover at an early phase of FCA arthritis in rats.     

Effects of acute and prolonged naphthalene exposure on brain monoaminergic neurotransmitters in rainbow trout (Oncorhynchus mykiss)

We have shown previously that acute (1 to 6 h) and prolonged (1 to 5 days) exposure of rainbow trout to naphthalene resulted in decreased plasmatic cortisol and 17-beta-estradiol levels. In order to elucidate the mechanisms through which naphthalene might disrupt endocrine regulation, the present study investigated whether brain monoaminergic neurotransmitters are altered by the action of this polycyclic aromatic hydrocarbon. In a first experiment, immature rainbow trout were injected with vegetable oil alone or containing naphthalene (10 and 50 mg/kg, i.p.), and sacrificed 1, 3 and 6 h after treatment. In a second experiment, slow-coconut oil implants alone or containing naphthalene (doses of 10 and 50 mg/kg) were i.p. located and fish sacrificed 1, 3 and 5 days after treatment. Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) were measured in several brain regions by HPLC. The results show that short-term naphthalene increases DA and 5-HT contents in hypothalamus and telencephalon, but differentially alter contents of the acid metabolites. Implants with naphthalene reduced DA content in hypothalamus and preoptic region but increased in telencephalon. 5-HT metabolism was decreased in hypothalamus, preoptic region, pituitary and brain stem after 3 to 6 days of treatment. In addition, the levels of NA were increased in hypothalamus and telencephalon after acute treatment and in hypothalamus and preoptic area after several days of exposure to naphthalene. These data suggest that brain neurotransmitter systems are sensitive to polycyclic aromatic hydrocarbons and could represent a target of the naphthalene-induced neuroendocrine disruption.     

Kinetics of Drug-Induced Changes in Dopamine and Serotonin Metabolite Concentrations in the CSF of the Rat

Cerebrospinal fluid (CSF) was removed at a constant flow rate of 1 microliter/min from the third ventricle of anesthetized rats. Every 15 min, CSF dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined by direct injection of CSF into a liquid chromatographic system coupled with electrochemical detection. Mean CSF concentrations of DOPAC, HVA, and 5-HIAA were 1.29 microM, 0.88 microM, and 2.00 microM, respectively. In order to determine the turnover rates of dopamine (DA) and serotonin, experiments using monoamine oxidase (MAO) inhibition were performed. Tranylcypromine (20 mg/kg i.p.) induced a sharp exponential decrease of CSF DOPAC, HVA, and 5-HIAA, with respective half-lives of 15.60 min, 16.91 min, and 77.23 min. Their respective turnover rates were 3.74, 2.22, and 1.18 nmol X ml-1 X h-1. m-Hydroxybenzylhydrazine (NSD-1015, 100 mg/kg i.p.) and monofluoromethyl-DOPA (100 mg/kg i.p.), two decarboxylase inhibitors, induced a slow exponential decrease of all three CSF metabolites. alpha-Methyl-p-tyrosine (250 mg/kg i.p.) also induced a slow exponential decrease of DOPAC and HVA. These decreases of CSF DOPAC and HVA induced by DA synthesis inhibitors may reflect the turnover of DA in vivo. Haloperidol (0.5 mg/kg i.p.) considerably enhanced CSF DOPAC and HVA without affecting 5-HIAA, confirming that dopaminergic receptors modulate DA neurotransmission in vivo. Haloperidol administered 1.5 h after NSD-1015 did not increase DOPAC and HVA, in contrast to reserpine (5 mg/kg i.p.) injected under the same conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of short-term cold exposure on pineal biosynthetic function in rats

In light of recent studies demonstrating stress-induced changes in pineal indoleamine metabolism, we tested the effect of acute cold stress on pineal biosynthetic function. Adult male rats were subjected to 30, 60, or 120 min of cold exposure (Ta = 2 degrees C) during either the light or dark phase of the daily photoperiodic cycle. Controls were kept at room temperature (22 +/- 2 degrees C). Animals were killed by decapitation and pineals were analyzed by radioimmunoassay for melatonin content and by radioenzymeassay for the activity of N-acetyltransferase (NAT). Cold exposure during the day elicited no significant changes in pineal indoleamine metabolism. Exposure to cold for 1 hr during the second hour after lights off slightly increased pineal melatonin content, without a concomitant change in NAT activity. Rats exposed to 2 hr of cold beginning 2 hr after lights off, however, displayed a 50% reduction in NAT activity, whereas pineal melatonin content remained unchanged. The paradoxical response of pineal NAT activity and melatonin content are not uncommon when rats are exposed to adverse stimuli.     

Injections of alpha-melanocyte stimulating hormone affect pineal serotonin, melatonin and N-acetyltransferase activity

To determine if exogenously administered alpha-melanocyte stimulating hormone (alpha-MSH) affects nighttime pineal N-acetyltransferase activity, pineal levels of 5-hydroxytryptophan, serotonin and melatonin, and plasma prolactin levels, adult male hamsters were injected at 1900 hr (lights out 2000-0600 hr) with two doses of the peptide and killed at 0300 hr. The low dose of alpha-MSH (200 ng) produced a significant fall in pineal serotonin, pineal NAT activity and plasma prolactin values. The high dose of the peptide (20 micrograms) increased circulating prolactin titers and pineal serotonin levels and caused a concomitant decrease in pineal melatonin levels.     

Alpha2-adrenoceptor mediated co-release of dopamine and noradrenaline from noradrenergic neurons in the cerebral cortex

Previous results suggest that extracellular dopamine (DA) in the rat cerebral cortex originates from dopaminergic and noradrenergic terminals. To further clarify this issue, dialysate DA, dihydroxyphenylacetic acid (DOPAC) and noradrenaline (NA) were measured both in the medial prefrontal cortex (mPFC) and in the occipital cortex (OCC), with dense and scarce dopaminergic projections, respectively. Moreover, the effect of the alpha2-adrenoceptor antagonist RS 79948 and the D2-receptor antagonist haloperidol on extracellular DA, DOPAC and NA was investigated. Extracellular DA and DOPAC concentrations in the OCC were 43% and 9%, respectively, those in the mPFC. Haloperidol (0.1 mg/kg i.p.) increased DA and DOPAC (by 35% and 150%, respectively) in the mPFC, but was ineffective in the OCC. In contrast, RS 79948 (1.5 mg/kg i.p.) increased NA, DA and DOPAC, both in the mPFC (by approximately 50%, 60% and 130%, respectively) and the OCC (by approximately 50%, 80% and 200%, respectively). Locally perfused, the DA transporter blocker GBR 12909 (10 micro m) was ineffective in either cortex, whereas desipramine (DMI, 100 micro m) markedly increased extracellular NA and DA in both cortices. The weak haloperidol effect on DA efflux was not enhanced after DA- and NA-transporter blockade, whereas after DMI, RS 79948 markedly increased extracellular NA, and especially DA and DOPAC in both cortices. The results support the hypothesis that most extracellular DA in the cortex is co-released with NA from noradrenergic terminals, such co-release being primarily controlled by alpha2-adrenoceptors.     

Sexual differences in the activity of periventricular-hypophysial dopaminergic neurons in rats.

The activities of periventricular-hypophysial dopaminergic (DA) neurons were compared in male and female rats by measuring dopamine synthesis (accumulation of 3,4-dihydroxyphenylalanine [DOPA] after inhibition of L-aromatic amino acid decarboxylase) and metabolism (concentrations of 3,4-dihydroxyphenylacetic acid [DOPAC]) in terminals of these neurons in the intermediate lobe of the pituitary. For comparison, the synthesis and metabolism of dopamine in the neural lobe of the pituitary and median eminence were also determined. The concentrations of DOPAC and accumulation of DOPA were higher in females than in males in both the intermediate lobe and median eminence, revealing a sexual difference in the basal activity of periventricular-hypophysial and tuberoinfundibular DA neurons. In contrast, there were no differences between male and female rats in activity of DA neurons terminating in the neural lobe. One week following gonadectomy, DOPA accumulation in the median eminence was decreased in females and increased in males, but remained unchanged in the intermediate lobe. These results indicate that sexual differences in the activity of periventricular-hypophysial DA neurons terminating in the intermediate lobe are not dependent upon the presence of circulating gonadal steroids, and in this respect, these neurons differ from tuberoinfundibular DA neurons.     

Dopaminergic innervation of the rainbow trout pituitary and stimulatory effect of dopamine on growth hormone secretion in vitro

To elucidate which factors regulate growth hormone (GH) secretion in rainbow trout, dopaminergic innervation of the rainbow trout pituitary along with the action of dopamine in vitro, were studied. Brains with attached pituitaries were double-labeled for putative dopaminergic neuronal fibers and somatotropes, using fluorescence immunohistochemistry. A direct dopaminergic innervation to the proximal pars distalis (PPD) with dopaminergic fibers terminating adjacent to somatotropes was demonstrated. Growth hormone secretion from whole pituitaries was measured in perifusate using a homologous GH-RIA. Dopamine (DA; 10(-7)-2x10(-6) g ml(-1)) increased basal GH secretion, with the GH secretion normalizing again after the DA exposure was halted. When pituitaries were pre-treated with somatostatin-14 (SRIF-14; 10(-12)-10(-9) g ml(-1)), before being exposed to different doses of DA, there was an inhibition of GH secretion which was not reversed after treatment of SRIF-14 was halted, unless DA was added. It is concluded that dopamine can function as a GH secretagogue in the rainbow trout pituitary gland.     

Difference in the reactivity of the mesocortical dopaminergic neurons to stress in the BALB/C and C57 BL/6 mice

The sensitivity to electric foot shock strees of the dopaminergic system projecting to the frontal cortex was investigated in Balb/c and C57 BL/6 mice. Changes in the activity of the dopaminergic neurons were estimated by measuring DOPAC and DA levels in the frontal cortex using a radioenzymatic method. The DOPAC/DA ratio was enhanced in both strains as soon as 2 min after the beginning of the strees but the effect was much more pronounced in the Balb/c than in the C57 BL/6 mice. The difference was even more important after 6 min of stress since the DOPAC/DA ratios were respectively 380 and 200% the corresponding control values. These changes were related both to an increase of DOPAC levels and a reduction of those of DA. This difference in the reactivity of the mesocortical dopaminergic neurons could partly contribute to some of the distinct behavioral responses of these two strains of mice. A preliminary communication of these results was made at the 7th International Congress of Pharmacology (Paris, July 1978).     

Exogenously administered and endogenously produced melatonin reduce hyperbaric oxygen-induced oxidative stress in rat lung

Hyperbaric oxygen (HBO) is a widely used treatment modality in many diseases. A known side effect of HBO is the production of reactive oxygen species. Many antioxidants such as vitamins C and E, riboflavin and selenium have been used successfully to scavenge the reactive oxygen species caused by HBO administration. In this study, we aimed to see if melatonin, a newly discovered antioxidant, has a protective effect against the overproduction of reactive oxygen species produced by HBO in rat lung tissue. Sixty male Sprague-Dawley rats were divided into 5 groups as follows: control, daytime HBO (3 ATA, 120 min), daytime HBO plus melatonin (10 mg/kg), nighttime HBO and nighttime HBO (under light exposure). The MDA, SOD and CAT levels of daytime and nighttime HBO (under light exposure) increased significantly. This significance was not found in the daytime HBO plus melatonin and nighttime HBO groups when compared with the control. In this study, HBO caused oxidant stress, and melatonin decreased the levels of MDA, SOD and CAT. Moreover, endogenous melatonin was found to be a more effective antioxidant than exogenous 10 mg/kg melatonin.     

Cholinergic mediation in the ventral tegmental area of alpha-melanotropin induced excessive grooming: changes of the dopamine activity in the nucleus accumbens and caudate putamen

The effect of alpha-melanotropin (alpha-MSH) on the rat mesolimbic dopaminergic activity was estimated by measuring the changes in dihydroxyphenyl acetic acid (DOPAC) and dopamine (DA) endogenous levels in the nucleus accumbens (Ac) and caudate putamen (CP). A marked increase of DOPAC/DA ratios resulting from an increase in DOPAC and decrease in DA levels was found in the Ac 30 and 65 min after bilateral alpha-MSH-injections (1 microgram) into the ventral tegmental area (VTA). Similar changes were observed in the CP 65 min post-injections. These peptide-induced changes were completely inhibited by a previous VTA injection of atropine (1 microgram), at a dose that totally blocked the alpha-MSH-induced excessive grooming and motor activation. These results confirms that alpha-MSH affects a cholinergic afferent to the VTA which modifies the mesolimbic dopaminergic system involved in the alpha-MSH/ACTH-induced behaviors.     

Pineal melatonin: circadian rhythm and variations during the hibernation cycle in the ground squirrel, Spermophilus lateralis

Variations in pineal melatonin content throughout a 24-hour period and during different phases of the hibernation bout cycle were studied in the golden-mantled ground squirrel (Spermophilus lateralis). In addition to pineal melatonin, the circadian variation in the activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were also investigated in summer animals maintained at 22 +/- 2 degrees C, on a light:dark (L:D) schedule of 12:12 hr for 1 month (lights on at 08.00 hr). Pineal glands were collected from six animals in each group at 1200, 1600, 2000, 2400, 0200, 0400, and 0800 hr. Changes in pineal melatonin content during the hibernation bout cycle were investigated in ground squirrels housed at 4 +/- .05 degrees C in relative darkness (1.9-3.4 lux; 10:14 LD). Pineal glands were obtained between 12:00 and 18:00 hr from 30 animals during one of three phases of the cycle (deep hibernation, euthermic interbout, and entrance into hibernation). Pineal melatonin was also measured for comparison in six winter euthermic animals that were housed at 22 +/- 2 degrees C, on a L:D schedule of 10:14 hr. Melatonin was measured in individual pineal glands by radioimmunoassay. The daily melatonin rhythm in S. lateralis was characterized by a marked increase in pineal melatonin during the dark phase, in which peak nighttime values were nearly 20-fold greater than daytime basal levels. The daily rhythm for NAT activity paralleled the changes in melatonin, showing a peak activity at 0200 hr that was 45 times greater than mean daytime values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of nocturnal increases in levels of melatonin elicits an anticipatory behavior in male quail

Abstract

During the reproductive development of male Japanese quail the duration of daily activity is prolonged and the onset of the rhythm of activity is advanced relative to the light‐dark cycle. The neuroendocrine basis for these changes was investigated with focusing on plasma levels of melatonin and testosterone. By means of 4 additional hours of photic stimulation of the brain, after the environmental lights (8L: 16D, lights on at 1000 hr) were turned off, the increase in levels of melatonin after lights‐off was suppressed for a few days. Thereafter the early onset of daily locomotor activity was observed and the gonads began to develop. Similar behavioral changes occurred in castrated quail following direct brain‐illumination or testosterone implants. The testosterone implants also suppressed the increases in levels of melatonin after lights‐off, for a few days. Treatment with an antiserum raised against melatonin (anti‐M) for the first 3 days, to suppress the increases in levels of melatonin after lights‐off, elicited such an anticipatory behavior. These results suggest that suppression of the nocturnal rise in melatonin levels is important for the first steps toward reproductive activity in male Japanese quail.     

Effects of Light on Dopamine Metabolism in the Chick Retina

The effect of prolonged exposure to light on the activity of dopaminergic neurons and dopamine (DA) metabolism of chick retinae was investigated. alpha-Fluoromethyldopa, a potent and specific irreversible inactivator of aromatic amino acid decarboxylase, was used to assess DA turnover after inhibition of synthesis, and also to assess in vivo tyrosine hydroxylase activity by dihydroxyphenylalanine accumulation. After 48 h of light exposure, retinal DNA in 12-day-old chicks was about 30% higher (p less than 0.005) whereas dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were elevated two to three times (p less than 0.005) the level of controls kept in the dark for the same period. DA turnover was about twofold faster in the light (t 1/2 = 31 min) than in the dark (t 1/2 = 65 min). Tyrosine hydroxylase, assayed in vitro with saturating levels of cofactor and substrate, increased by about 50% after light exposure. The apparent tyrosine hydroxylase activity in vivo was approximately sixfold higher in the light than the dark. These results are interpreted and discussed in terms of the regulation of DA synthesis, and the use of DOPAC and HVA as indices of DA function in the retina.     

Plasma Melatonin Levels in Relation to the Light-Dark Cycle and Parental Background in Domestic Pigs

To study porcine melatonin secretion in a stable environment 3 daytime (10.00 – 15.00) and 3 nighttime (22.00 – 03.00) plasma samples were collected by jugular venipuncture from 15 gilts, 16 sows, 3 boars and 48 piglets (24 females and 24 males from 8 litters) and analysed for melatonin content. Nighttime melatonin concentrations were higher than daytime melatonin concentrations (p < 0.001), whereas no effect of sampling order could be discerned. The 3 adult Hampshire boars had higher melatonin concentrations during the day and the night, than the 31 adult Yorkshire females (p < 0.05). There was no clear difference between gilts and sows in plasma melatonin. The gilts from one of the litters had higher plasma melatonin concentrations than the gilts in 3 other litters (p < 0.05). Among the 48 piglets, the increase of nocturnal melatonin secretion differed between litters (p < 0.01), whereas the influence of father was not quite significant (p = 0.12). No difference in daytime melatonin concentrations between litters could be found, and there was no difference in melatonin levels between the male and female piglets. In conclusion, this study demonstrates that domestic pigs express a nocturnal increase of melatonin secretion in a standard stable environment. For some animals the amplitude of nighttime melatonin secretion was very low, although always higher than the daytime base levels. Furthermore, the levels of nighttime melatonin secretion differed between litters, which suggests a genetic background.     

Effects of alterations in the activity of tuberohypophysial dopaminergic neurons on the secretion of alpha-melanocyte stimulating hormone

Administration of gamma-butyrolactone (GBL), an anesthetic which reduces dopaminergic neuronal activity, decreased the concentration of the dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the intermediate lobe of the pituitary gland, and increased alpha-melanocyte stimulating hormone (alpha MSH) concentrations in the serum of male rats. Bilateral electrical stimulation of the rostral arcuate nucleus, which contains perikarya of tuberohypophysial DA neurons, increased DOPAC concentrations in the intermediate lobe and decreased alpha MSH concentrations in the serum of GBL-anesthetized rats. Administration of the DA antagonist haloperidol prevented the decline in serum alpha MSH levels following arcuate nucleus stimulation, but had no effect on serum alpha MSH concentrations in sham-stimulated GBL-treated rats. These results indicate that GBL-induced decreases or stimulation-induced increases in the activity of tuberohypophysial DA neurons are accompanied by corresponding changes in the metabolism of DA in the intermediate lobe of the rat pituitary gland, and by reciprocal changes in the secretion of alpha MSH.     

Propentophylline increases striatal dopamine release but dampens methamphetamine-induced dopamine dynamics: A microdialysis study

While there are currently no medications approved for methamphetamine (METH) addiction, it has been shown that propentofylline (PPF), an atypical methylxanthine, can suppress the rewarding effects of methamphetamine (METH) in mice. This experiment studied the interactions of PPF with METH in striatal dopaminergic transmission. Herein, the impact of PPF (10–40 mM, intrastriatally perfused (80 min) on the effect of METH (5 mg/kg, i.p.) on striatal dopamine (DA) release was evaluated using brain microdialysis in Sprague–Dawley adult rats. METH was injected at the 60 min time point of the 80 min PPF perfusion. The extracellular levels of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined using high performance liquid chromatography with electrochemical detection (HPLC-ED). PPF induced a concentration-dependent increase in DA release beginning 30 min after the onset of PPF perfusion. DA peak levels evoked by 40 mM PPF were similar to those induced by 5 mg/kg METH i.p. Only the highest concentration of PPF decreased the METH-induced DA peak (circa 70%). The significant decreases in extracellular levels of DOPAC and HVA evoked by METH were partially blocked by 10 and 20 mM PPF. Although 40 mM of PPF also partially blocked the METH-induced DOPAC decrease, it completely blocked HVA depletion after a transient increase in HVA levels in METH-treated rats. Data indicates for the first time that while PPF increases presynaptic striatal DA dynamics it attenuates METH-induced striatal DA release and metabolism.     

Activation of Melatonin Receptor Sites Retarded the Depletion of Norepinephrine Following Inhibition of Synthesis in the C3H/HeN Mouse Hypothalamus

The aim of the present study was to determine the effect of activation of melatonin receptor sites on the activity of noradrenergic neurons in the C3H/HeN mouse brain. Changes in noradrenergic activity were assessed by measuring norepinephrine (NE) levels in the hypothalamus, frontal cortex, and hippocampus following inhibition of NE synthesis with alpha-methyl-p-tyrosine (alpha-MpT) (300 mg/kg, i.p., 2 h). 6-Chloromelatonin (1-30 mg/kg, i.p.) significantly retarded the alpha-MpT-induced decrease in NE levels in the hypothalamus, but not in hippocampus and frontal cortex. This effect was observed at 30 min and 60 min after 6-chloromelatonin administration and was dose dependent. At noon, when the levels of endogenous melatonin are low, the melatonin receptor antagonist luzindole (30 mg/kg, i.p., 30 min) did not affect the depletion of NE by alpha-MpT; however, it (1-30 mg/kg) completely antagonized the 6-chloromelatonin-induced reduction of NE depletion elicited by alpha-MpT in hypothalamus. These results suggest that activation of melatonin receptor sites in brain of C3H/HeN mouse retarded the depletion of NE elicited by alpha-MpT. At midnight, when the levels of melatonin are high, luzindole (30 mg/kg) significantly accelerated the depletion of NE by alpha-MpT in hypothalamus, but not in frontal cortex or hippocampus, suggesting activation of melatonin receptor sites by endogenous melatonin. We conclude that activation of melatonin receptor sites in C3H/HeN mouse brain by endogenous melatonin inhibits the activity of noradrenergic neurons innervating the hypothalamus.