Brain monoamines and sexual behavior in Japanese quail: Effects of castration and steroid replacement therapy

In the male Japanese quail, testosterone is required for the activation of sexual behavior. This steroid dependent process may rely heavily on mediation via monoaminergic neurons. These experiments were conducted to study the relationship between reproductive state (hormonal and behavioral components) and levels of monoamines in selected areas of the brain in Japanese quail. In Experiment 1, monoamine levels in a number of brain areas were compared in castrates, testosterone-implanted castrates, and intact males. Monoamine levels were comparable to those previously measured in Japanese quail, and there were no significant differences due to treatment. Plasma luteinizing hormone (LH) levels and recovery of cloacal gland area in implanted castrates confirmed the afficacy of treatments. In Experiment 2, the disappearance of dopamine (DA) and norepinephrine (NE) following administration of a-methyl-para-tyrosine (aMPT) was used as an indicator of turnover rate. Male and female quail were gonadectomized at 3 weeks of age. At the age of five weeks, some gonadectomized males and females were given implants containing testosterone. Only intact males and testosterone-implanted castrated males showed reproductive behavior. Plasma gonadotropin levels were elevated in gonadectomized birds and reduced in steroid-implanted gonadectomized birds. The aMPT treatment significantly reduced the levels of DA and NE in the telecephalon and the level of DA in the hypothalamus. After aMPT treatment, the disappearance of NE in the telecephalon and of DA in the hypothalamus were significantly different according to the sex or treatment of the birds or both. Significant interactions between these two factors were observed. Disappearance rate of NE in the telecephalon was decreased by castration of males and increased by ovariectomy of females. Both effects were counteracted by testosterone. Reverse effects were observed for DA disappearance in the hypothalamus (increase with castration in males and decrease with ovariectomy in females). These results give evidence for altered aminergic function in specific areas of the brain relative to altered reproductive state.     

Angiotensin II-norepinephrine relationship in the central nervous system

The effects of angiotensin II (AII) and bilateral nephrectomy on [3H] norepinephrine (NE) uptake in hypothalamus and medulla oblongata were studied in male rats. The endogenous NE content in hypothalamus increased 4, 24 and 48 h after nephrectomy with a simultaneous decreasing of plasma renin activity. Intraventricularly infused [3H] NE uptake increased in hypothalamus and medulla oblongata of nephrectomized animals in cytoplasmatic compartment as in granular stores, while it decreased in hypothalamus of AII-infused animals. [3H] NE metabolites radioactivity decreased in nephrectomized animals if they are compared with AII-infused ones. These changes were independent of systolic arterial pressure that was not modified in none of the groups. The study of the ratio granular/cytoplasmatic [3H] NE and metabolites radioactivity shows that AII probably acts on cellular membrane uptake of NE. The modification of metabolites/NE ratio in both stores would be due to AII action on MAO activity. The effects of AII and nephrectomy on [3H] NE uptake can explain the inverse relationship between circulating AII levels and NE content in the central nervous system (CNS).     

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.     

Atrial natriuretic factor inhibits norepinephrine biosynthesis and turnover in the rat hypothalamus

We have previously reported that atrial natriuretic factor (ANF) increased neuronal norepinephrine (NE) uptake and reduced basal and evoked neuronal NE release. Changes in NE uptake and release are generally associated to modifications in the synthesis and/or turnover of the amine. On this basis, the aim of the present work was to study ANF effects in the rat hypothalamus on the following processes: endogenous content, utilization and turn-over of NE; tyrosine hydroxylase (TH) activity; cAMP and cGMP accumulation and phosphatidylinositol hydrolysis. Results showed that centrally applied ANF (100 ng/microl/min) increased the endogenous content of NE (45%) and diminished NE utilization. Ten nM ANF reduced the turnover of NE (53%). In addition, ANF (10 nM) inhibited basal and evoked (with 25 mM KCl) TH activity (30 and 64%, respectively). Cyclic GMP levels were increased by 10 nM ANF (100%). However, neither cAMP accumulation nor phosphatidylinositol breakdown were affected in the presence of 10 nM ANF. The results further support the role of ANF in the regulation of NE metabolism in the rat hypothalamus. ANF is likely to act as a negative putative neuromodulator inhibiting noradrenergic neurotransmission by signaling through the activation of guanylate cyclase. Thus, ANF may be involved in the regulation of several central as well as peripheral physiological processes such as cardiovascular function, electrolyte and fluid homeostasis, endocrine and neuroendocrine synthesis and secretion, behavior, thirst, appetite and anxiety that are mediated by central noradrenergic activity.     

Further investigation of the role of progesterone in the control of embryo transport in the mouse

Combined ovariectomy and adrenalectomy retarded mouse embryo transport while either operation alone did not. Serum progesterone levels were reduced after ovariectomy and after the combined operation but detectable levels were still present on Day 4 following both procedures. Embryo transport was also retarded after administration of testosterone propionate. This effect was abolished by progesterone and was not mimicked by 5 alpha-dihydrotestosterone. From these results it is concluded that progesterone influences embryo transport and that androgenic effects are probably a result of antagonism of progesterone.     

卵巢激素撤除诱发雌性小鼠抑郁样状态（英文）

目的：建立卵巢激素撤除诱发雌性小鼠抑郁样状态模型,并且探讨其可能的神经化学机制。方法：将小鼠分为假手术组,卵巢摘除组,己烯雌酚治疗组和氟西汀治疗组。动物行卵巢摘除术后开始给药,术后两周进行强迫游泳试验及悬尾试验以考察其抑郁样状态,并利用高效液相结合电化学检测测定下丘脑及海马中去甲肾上腺素（NE）、多巴胺（DA）以及五羟色胺（5-HT）的含量。结果：在强迫游泳试验及悬尾试验中,卵巢摘除小鼠较假手术组小鼠不动时间显著延长。神经递质测定显示,卵巢摘除小鼠下丘脑中NE与DA的含量显著降低,海马中NE与5-HT的含量显著降低。给予己烯雌酚或氟西汀治疗对抗了卵巢摘除所诱导的抑郁样状态,并且缓解了神经递质水平的下降。结论：双侧卵巢摘除诱发的小鼠抑郁样状态可以模拟妇女更年期抑郁的某些症状。本研究对于探讨卵巢激素撤除诱发抑郁状态的神经生化机制可能具有重要的意义。     

Modifications of arterial pressure and plasma renin: their effects on the norepinephrine content of hypothalamus and medulla oblongata.

The effects of the bilateral nephrectomy and acute hypotension caused by the cava vein ligature on the norepinephrine (NE) concentration in hypothalamus and medulla oblongata and on the plasma renin activity were studied in male rats. NE increased and plasma renin activity decreased in hypothalamus in 24 h nephrectomized rats with or without the ligatures of the cava vein. NE also decreased in medulla of groups with the ligatures only. The mean arterial pressure, did not correlate with the NE or plasma renin activity levels. The modifications of the NE in the central nervous system showed an inverse relationship with plasma renin activity and this, could be due to changes in the NE uptake and/or release caused by the plasma renin activity alterations. NE modifications do not seem to be caused directly through reflex of the arterial pressure.     

Cadmium effects on hypothalamic-pituitary-testicular axis in male rats

This study analyzes cadmium effects at the hypothalamic-pituitary-testicular axis. Male rats were given cadmium during puberty or adulthood. Cadmium exposure through puberty increased norepinephrine content in all hypothalamic areas studied, but not in the median eminence. Metal exposure increased serotonin turnover in median eminence and the anterior hypothalamus, while decreased it in mediobasal hypothalamus. Also, decreased plasma levels of testosterone were found. Cadmium exposure during adulthood increased norepinephrine content in posterior hypothalamus and decreased the neuro-transmitter content in anterior and mediobasal hypothalamus. Decreased circulating levels of luteinizing hormone (LH) and testosterone and increased plasma follicle stimulating hormone (FSH) levels were also observed. Cadmium accumulated in all analyzed tissues. Various parameters showed age-dependent changes. These data suggest that cadmium globally effects hypothalamic-pituitary-testicular axis function by acting at the three levels analyzed and that an interaction between cadmium exposure and age emerge.     

Effect of testosterone on oxidative stress and cell damage induced by 3-nitropropionic acid in striatum of ovariectomized rats

This paper evaluates the effects of testosterone (0.5 mg/kg subcutaneously (s.c.) for 8 days) on oxidative stress and cell damage induced by 3-nitropropionic acid (20 mg/kg intraperitoneally (i.p.) for 4 days) in ovariectomized rats. Gonadectomy triggered oxidative damage and cell loss, evaluated by the detection of caspase-3, whereas 3-nitropropionic acid increased the levels of oxidative stress induced by ovariectomy and prompted cell damage characterized by enhanced levels of lactate dehydrogenase. These changes were blocked by testosterone administration. Our results support the following conclusions: i) ovariectomy triggers oxidative and cell damage via caspase-3 in the striatum; ii) 3-nitropropionic acid exacerbates oxidative stress induced by ovariectomy and leads to cell damage characterized by increased levels of lactate dehydrogenase; iii) testosterone administration decreases oxidative stress and cell damage. Additionally, these data support the hypothesis that testosterone might play an important role in the onset and development of neurodegenerative diseases.     

自发性高血压大鼠中枢血管紧张素Ⅱ的变化对中枢肾上腺素...

The content of norepinephrine (NE) and epinephrine (E) in the brain of spontaneously hypertensive rats has proved abnormal, but the cause remained unknown. It was shown in the recent work that NE content in pons, posterior hypothalamus, nucleus caudatus and E concentration in medulla oblongata, anterior and posterior hypothalamus of 12-week old stroke-prone spontaneously hypertensive rats (SHRSP) were much higher than those of age-matched Wister-Kyoto rats (WKY). SHRSP also showed higher levels of systolic blood pressure (SBP) and brain angiotensin II (A II) than WKY. Intracerebroventricular (icv) perfusion of angiotensin-converting enzyme inhibitor captopril (20 micrograms for each time and three times for each day for four weeks) inhibited the synthesis of brain A II and reduced SBP and NE, E contents in all examined brain areas in SHRSP and WKY. However, the effects of chronically perfused captopril on SBP and brain NE, E levels in SHRSP were much more significant than in WKY. The results indicate that the modulatory effects of central renin-angiotensin system (RAS) on central adrenergic and noradrenergic system might be overactivated in SHRSP, which might partially responsible for the abnormally high levels of NE, E in some of the brain areas of SHRSP.     

Adrenergic activity in hypothalamus and ovulation

The turnover of norepinephrine (NE) and its synthesis in the hypothalamus in rats just prior to and subsequent to ovulation was studied. Hypothalamic NE concentration in proestrus (preovulatory) was higher than in estrus rats (3.48 plus or minus) .09 mcg/gm vs. 2.13 plus or minus .04 mcg/gm). When methylester hydrochloride (MPT), a blocker of catecholamine biosynthesis, was injected, proestrus rats NE dropped 62% vs. estrus rats' drop of 28.6%. Tritiated NE injected to show synthesis rates showed a higher rate of NE synthesis produced in the hypothalamus during proestrus vs. estrus. In addition there was an increase in NE levels between diestrus Day 2 and proestrus localized to the anterior and middle hypothalamus.     

Neurokinin A in the anterior pituitary of female rats: effects of ovariectomy and estradiol.

The effect of acute and chronic ovariectomy and the substitutive treatment with 17-beta estradiol and/or progesterone on anterior pituitary levels of neurokinin A (NKA) was studied in female rats. Acute ovariectomy did not result in significant changes of NKA in the anterior pituitary gland as compared with the levels in diestrous intact rats, but a single injection of 5 micrograms of estradiol in ovariectomized rats significantly decreased NKA levels in the anterior pituitary gland. Progesterone was without effect and did not modify the decrease of NKA in the anterior pituitary gland induced by estradiol. In rats examined 11 to 17 days after ovariectomy, NKA in the anterior pituitary gland was significantly higher than in diestrous intact rats. In the hypothalamus, ovariectomy resulted in decreased levels of NKA in the median eminence-arcuate nucleus. Estradiol significantly reduced NKA stores in the anterior pituitary gland but increased them in the whole hypothalamus and in the median eminence-arcuate nucleus. Thus, estradiol seems to be a powerful regulator of NKA stores in the adenohypophysis and also in the hypothalamus.     

Feeding increases 5-hydroxytryptamine and norepinephrine within the hypothalamus of chicks

It is thought that hypothalamic 5-hydroxytryptamine (5HT) and norepinephrine (NE) are involved in the regulation of feeding in chicks. The present study was conducted to elucidate changes in the levels of extracellular 5HT and NE in the hypothalamus during feeding of chicks. In order to measure 5HT, NE and 4-hydroxy-3-methoxyphenylglycol (MHPG), which is a major metabolite of NE, we used brain microdialysis and high-pressure liquid chromatography with an electrochemical detector. After collecting samples to determine the basal levels of 5HT, NE and MHPG, food-deprived birds were given access to food. 5HT levels in the medial hypothalamus (MH) and lateral hypothalamus (LH) increased during the first 30 min of feeding, and then returned to basal levels. NE and MHPG in the LH increased during feeding, and remained elevated throughout the experiment. This study supports an idea that hypothalamic monoamines in the chick brain are involved in the regulation of feeding.     

Effects of gonadectomy and sex hormones on the levels of noradrenaline and dopamine in rat hypothalamus

The levels of noradrenaline and dopamine were determined in the homogenates of the hypothalamus of rats of either sex. The determinations were done in intact rats, after sham gonadectomy, 6 and 9 weeks after gonadectomy, and in gonadectomized rats receiving 6 weeks after gonadectomy one dose of oestradiol cypionate (females) or testosterone cypionate (males). Catecholamines were determined fluorimetrically. The changes of the determined catecholamines differed in the hypothalamic homogenates in males and females after gonadectomy. Following orchidectomy the noradrenaline level rose, while after ovariectomy the level of this catecholamine decreased. Contrary to this, in ovariectomized rats the dopamine level was significantly raised after the operation. This change was reversible as observed after administration of oestradiol cypionate. Orchidectomy and testosterone cypionate injection had no effect on the dopamine level in the hypothalamus. The role of these catecholamines in the processes connected with the regulation of the hypothalamus-hypophysis-gonad axis is discussed.     

Neurotransmitter-controlled steroid hormone receptors in the central nervous system

Results are discussed indicating that neurotransmitters affect steroid hormone activity not only by controlling via neuroendocrine events the hypophysial-gonadal and hypophysial-adrenal axes, but also by modulating cell responsiveness to steroids in target cells. Hyper- or hypoactivity of pineal nerves result in enhancement or impairment of estradiol and testosterone effects on pineal metabolism in vivo and in vitro. Pineal cytoplasmic and nuclear estrogen and androgen receptors are modulated by norepinephrine released from nerve endings at the pinealocyte level. Neural activity affects the cycle of depletion-replenishment of pineal estrogen receptors following estradiol administration. Another site of modulation of steroid effects on the pinealocytes is the intracellular metabolism of testosterone and progesterone; nerve activity has a positive effect on testosterone aromatization and a negative effect on testosterone and progesterone 5α-reduction. NE activity on the pineal cells is mediated via β-adrenoceptors and cAMP. In the central nervous system information on the neurotransmitter modulation of steroid hormone action includes the following observations: (a) hypothalamic deafferentation depresses estrogen receptor levels in rat medial basal hypothalamus; (b) changes in noradrenergic transmission affect, via α-adrenoceptors, the estradiol-induced increase of cytosol progestin receptor concentration in guinea pig hypothalamus; (c) cAMP increases testosterone aromatization in cultured neurons from turtle brain; (d) electrical stimulation of dorsal hippocampus augments, and reserpine or 6-hydroxydopamine treatment decrease, corticoid binding in cat hypothalamus. In the adenohypophysis changes in dopaminergic input after median eminence lesions or bromocriptine treatment of rats result in opposite modifications of pituitary estrogen receptor levels. Therefore all these observations support the view that neurotransmitters can modulate the attachment of steroid hormones to their receptors in target cells.     

Effects of a major androgen-dependent urinary protein, alpha 2u-globulin on the pituitary-gonadal axis and hypothalamic monoamines in adult male mice.

The purpose of the present study was to evaluate the effects of alpha-2u-globulin, a sex-dependent male rat urinary protein on pituitary-gonadal functions and hypothalamic monoamine contents in male mice. Adult male mice, maintained under standardized laboratory conditions (L:D, 14:10) were injected subcutaneously with alpha-2u-globulin at a dose of 1 mg/animal/day or with vehicle daily for 14 days and killed 16 h after the last injection. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and testicular levels of T were measured by radioimmunoassays. The concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in medial basal hypothalamus (MBH) and anterior hypothalamus (AH) were measured by high performance liquid chromatography. Administration of alpha-2u-globulin led to a significant increase in plasma FSH and LH levels (P less than 0.05) as well as in plasma and testicular T levels (P less than 0.025). In the MBH of alpha-2u-globulin treated mice, there were significant elevations of NE (P less than 0.025), DA (P less than 0.01) and 5-HT (P less than 0.025) contents. In the AH, both DA (P less than 0.025) and 5-HT (P less than 0.01) contents were decreased while NE content remained unaltered. These results indicate that administration of alpha-2u-globulin can lead to a significant stimulation of pituitary-testicular axis and that this effect may be mediated through alteration of hypothalamic monoamines.     

Acute effects of acephate and methamidophos and interleukin-1 on corticotropin-releasing factor (CRF) synthesis in and release from the hypothalamus in vitro

Acute effects of Ace, Meth and IL-1 on AChE activity, ACh and CRF mRNA levels in, and CRF-release from the hypothalamus were studied in vitro. The hypothalamus samples were dissected from the rat brain and were incubated in vitro with IL-1, Ace or Meth in the presence or absence of Dex, Atrop, PTL, PROP and GABA. Ace and Meth, but not IL-1, inhibited AChE activity, while all three compounds; (1) increased ACh and CRF mRNA levels in and CRF release from; (2) activated the CRE promoter region of CRF-gene in: and (3) increased cFos binding to the AP-1 region of the CRF-gene in the hypothalamus. Dex suppressed the effects of IL-1, possibly by inducing the nGRE regulatory sites of the CRF-gene. Dex, however, did not modulate the effects of Ace and Meth on the hypothalamus, which may be attributed to the failure of Dex to modulate the CRF-gene's nGRE regulatory sites. Atrop caused 80-90% inhibition of the effects of IL-1, but caused only 50-65% inhibition of the effects of Ace or Meth on CRF mRNA levels in and CRF release from the hypothalamus. PTL did not affect, while PROP slightly attenuated the effects of IL-1 and the insecticides on the hypothalamus. GABA attenuated the effects of the insecticides but not the effects of IL-1 on the hypothalamus. This suggests that the IL-1-induced augmentation of CRF synthesis in and release from the hypothalamus is mediated through a cholinergic pathway, while the insecticide-induced augmentation of CRF synthesis in and release from the hypothalamus is mediated through the cholinergic and GABAergic pathways. The insecticides, but not IL-1, disrupt feedback regulation of CRF synthesis in and release from the hypothalamus.     

Ovariectomy causes cell proliferation and matrix synthesis in the growth plate cartilage of the adult rat

The in vivo effects of ovariectomy in rats have been studied on cell proliferation and matrix synthesis in the growth plate cartilage by assessing immunohistochemically the levels of proliferating cell nuclear antigen and chondroitin sulphate proteoglycan(s). The serum levels of insulin-like growth factor-I and growth hormone were also measured by radioimmunoassay procedures. At 5 weeks after ovariectomy, the serum levels of the growth factor were significantly higher than those in sham-operated rats. In contrast, the level of growth hormone was lower. The nuclear staining of proliferating cell nuclear antigen was generally seen in the zone of proliferative chondrocytes from both groups of rats. Whereas almost all chondrocytes in the proliferative zone of ovariectomized rats expressed proliferating cell nuclear antigen immunoreactivity, fewer did so in that of the sham rats. Quantitative image analysis by ACAS 570 laser cytometry demonstrated that the n uclear antigen-positive sites in ovariectomized rats had significantly higher integrated values (staining intensity), areas and perimeters than those in sham rats. In addition, the number of chondroitin sulphate proteoglycan-immunoreactive cells in the proliferative chondrocytes was also higher in ovariectomized rats than in sham ones. These results suggest that ovariectomy significantly stimulates the cell proliferation and matrix synthesis in the growth plate cartilage, probably through the higher serum level of insulin-like growth factor-I.     

Estrogen-androgen antagonism in the regulation of epidermal growth factor in mouse submandibular salivary gland and kidneys

To eludicate hormonal regulation of epidermal growth factor (EGF) concentration we studied the effects in adult female mice of ovariectomy and postovariectomy treatments with testosterone plus estradiol on the EGF concentrations in submandibular salivary gland (SMG), plasma, kidneys and urine. In the tissues, we also studied the location of EGF immunohistochemically and measured EGF mRNA. After ovariectomy, SMG EGF first decreased to one third of preovariectomy level. After postovariectomy day 10 it started to increase and reached by day 80 3.5-fold the preovariectomy level. Simultaneously, EGF mRNA increased. Testosterone treatment further strongly augmented the levels of both EGF mRNA and EGF. A small dose of estradiol counteracted slightly the mRNA effect of testosterone. After ovariectomy plasma EGF first increased 1.3-fold by day 10, then returned to the initial levels, and rose again 1.6-fold by day 80. Testosterone treatment induced a further 1.5-fold increase. Estradiol did not counteract this effect. Kidney EGF decreased 15% by postovariectomy day 20. This was preceded by a decrease in EGF mRNA from day 10 onwards. The EGF concentration recovered during the 80 days, but the EGF mRNA level stayed low. Testosterone treatment further reduced the levels of both EGF mRNA and EGF. This effect was counteracted by estradiol. Urine EGF increased after ovariectomy to a peak (1.7-fold) by day 40. It then returned to the preovariectomy levels by day 80. Testosterone treatment increased urinary EGF 1.9-fold; concomitant estradiol had no effect.     

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.