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1.
Brain Res Bull ; 54(6): 675-80, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11403995

ABSTRACT

The direct effects of L-deprenyl, a monoamine oxidase inhibitor, on the hypothalamus of male Sprague-Dawley rats was investigated by measuring the efflux of norepinephrine (NE), dopamine (DA), serotonin (5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) using a combination of high performance liquid chromatography with electrochemical detection and an in vitro incubation system. After measuring basal efflux by incubating the hypothalami with Krebs-Ringers Henseleit (KRH) alone during the first incubation period, hypothalami were incubated either with the medium, KRH alone (0 mM), or KRH containing 0.1, 1, and 10 mM L-deprenyl. During the third incubation period, hypothalami were again incubated with KRH alone to measure the residual effects if any. During the final incubation period, the hypothalami were stimulated with high K(+) KRH. Deprenyl produced a dose-dependent increase in the efflux of NE, DA, and 5-HT from the hypothalami. Neurotransmitter efflux returned to pretreatment levels when L-deprenyl was removed from the medium. In contrast to NE, DA, and 5-HT, the efflux of the metabolites DOPAC and 5-HIAA was inhibited in a dose-dependent fashion after incubation with L-deprenyl. Results from this study demonstrate that L-deprenyl is capable of stimulating the efflux of neurotransmitters in vitro by a direct action on the hypothalamus.


Subject(s)
Biogenic Monoamines/metabolism , Hypothalamus/drug effects , Monoamine Oxidase Inhibitors/pharmacology , Neurons/drug effects , Selegiline/pharmacology , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Dopamine/metabolism , Dose-Response Relationship, Drug , Hydroxyindoleacetic Acid/metabolism , Hypothalamus/cytology , Hypothalamus/metabolism , Male , Neurons/cytology , Neurons/metabolism , Norepinephrine/metabolism , Rats , Rats, Sprague-Dawley , Serotonin/metabolism
2.
J Neuroendocrinol ; 13(3): 261-9, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11207940

ABSTRACT

The purpose of this study was to investigate the age-related changes in the responsiveness of tuberoinfundibular dopamine (TIDA) neurones to chronic hypoprolactinemia induced by treatment with bromocriptine, a dopamine receptor agonist. In one experiment, TIDA neuronal activity after acute hypoprolactinemia or exogenous prolactin was monitored by measuring tyrosine hydroxylase (TH) activity in the stalk median eminence of middle-aged cycling female rats (10-12 months), old constant oestrous rats (18-20 months) and old pseudopregnant rats (22-24 months). In another experiment, middle-aged cycling (10-12 months) rats were treated with bromocriptine for 6 or 12 months. TH activity was measured in the stalk median eminence, TH mRNA levels were measured in the arcuate nucleus and dopamine concentrations were measured in the arcuate nucleus and median eminence. Responsiveness of TIDA neurones to exogenous prolactin and to the withdrawal of bromocriptine in these rats was also tested. While the TIDA neurones in all three age groups responded to acute hypoprolactinemia by showing a reduction in TH activity, older rats failed to respond to exogenous prolactin administration. In contrast, chronic hypoprolactinemia for 12 months enabled the rats to retain TIDA neuronal responsiveness to exogenous prolactin. It also decreased TIDA neuronal function as measured by dopamine concentrations in the median eminence, TH activity in the stalk median eminence and TH mRNA in the arcuate nucleus of ageing rats. The restoration of the responsiveness of these neurones to prolactin stimulation in older rats demonstrates for the first time that hypoprolactinemia produced by chronic bromocriptine treatment indeed provides a neuroprotective effect on TIDA neurones. These results indicate that maintaining a low level of neuronal activity by lowering prolactin levels may be a contributing factor in retaining the plasticity of TIDA neurones.


Subject(s)
Aging , Bromocriptine/pharmacology , Dopamine/metabolism , Median Eminence/drug effects , RNA, Messenger/analysis , Tyrosine 3-Monooxygenase/genetics , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Arcuate Nucleus of Hypothalamus/drug effects , Arcuate Nucleus of Hypothalamus/metabolism , Dopamine Agonists/pharmacology , Estrus , Female , Gene Expression/drug effects , Hyperprolactinemia/chemically induced , Hyperprolactinemia/metabolism , Median Eminence/metabolism , Neuronal Plasticity , Prolactin/pharmacology , Pseudopregnancy , Rats , Rats, Sprague-Dawley , Tyrosine 3-Monooxygenase/metabolism
3.
Neurosci Lett ; 284(3): 159-62, 2000 Apr 28.
Article in English | MEDLINE | ID: mdl-10773423

ABSTRACT

Lipopolysaccharide (LPS) is known to produce a number of central and neuroendocrine effects but the mechanisms involved are still unclear. This study was done to investigate the possibility that LPS-induced fever and activation of central monoamines are mediated through the vagus. Adult male rats were subjected to sub-diaphragmatic vagotomy (SDV), or sham operation and treated with saline or LPS in saline (10 microg/kg bw) 2 h later. Rectal temperature was monitored at half-hourly intervals for 5 h after which the animals were sacrificed and monoamine concentrations in hypothalamic nuclei were measured using HPLC-EC. SDV delayed the rise in rectal temperature induced by LPS by 1 h when compared to Sham animals. It also increased the concentrations of monoamines in the paraventricular nucleus of both Sham and SDV rats. This indicates that routes other than the vagus probably mediate LPS' actions on the central nervous system.


Subject(s)
Biogenic Monoamines/metabolism , Fever/chemically induced , Lipopolysaccharides/pharmacology , Paraventricular Hypothalamic Nucleus/metabolism , Vagus Nerve/physiology , Animals , Body Temperature , Chromatography, High Pressure Liquid , Dopamine/metabolism , Fever/metabolism , Fever/physiopathology , Male , Norepinephrine/metabolism , Paraventricular Hypothalamic Nucleus/drug effects , Paraventricular Hypothalamic Nucleus/physiopathology , Rats , Rats, Sprague-Dawley , Serotonin/metabolism , Time Factors , Vagotomy , Vagus Nerve/drug effects , Vagus Nerve/surgery
4.
Endocrine ; 10(3): 225-32, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10484286

ABSTRACT

Previously, we have reported that L-deprenyl decreased the incidence of mammary tumors and pituitary tumors in old acyclic rats. The objective of the present study was to investigate the effects of L-deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, treatment on the development and growth of tumors and on the metabolism of catecholamines and indoleamine in the medial basal hypothalamus (MBH) and the striatum (ST) of rats bearing 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors. Female Sprague-Dawley rats with DMBA-induced mammary tumors were injected (sc) daily with 0.25 mg or 5.0 mg of deprenyl/kg BW or the vehicle (saline; control) for 12 wk. Tumor diameter, tumor number, body weight, and feed intake were measured every week of the treatment period. Serum PRL and the concentrations of catecholamines, indoleamine, and their metabolites were measured by RIA and HPLC, respectively. Treatment with 5.0 mg deprenyl decreased the tumor diameter, tumor number, and serum prolactin (PRL) level. Although the body weight increased in all three groups, the body weight gain in the 5.0 mg group was smaller than that in the control and 0.25 mg groups. Deprenyl treatment had no effect on feed intake. The concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were decreased in the MBH and the ST, and the concentration of 5-hydroxyindoleacetic acid (5-HIAA) was decreased in the MBH of deprenyl-treated rats. Treatment with 5.0 mg deprenyl enhanced the concentrations of norepinephrine (NE) and serotonin (5-HT) in the MBH and in the ST, and the concentration of dopamine (DA) in the MBH. These results suggest that the suppression of the development and growth of DMBA-induced mammary tumors by chronic deprenyl treatment may be mediated through alterations in the synthesis and metabolism of catecholamines and indoleamine in the MBH and inhibition of PRL secretion.


Subject(s)
Biogenic Monoamines/metabolism , Brain/metabolism , Mammary Neoplasms, Experimental/pathology , Monoamine Oxidase Inhibitors/pharmacology , Prolactin/blood , Selegiline/pharmacology , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Body Weight , Dopamine/metabolism , Eating , Female , Homovanillic Acid/metabolism , Hydroxyindoleacetic Acid/metabolism , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/metabolism , Monoamine Oxidase Inhibitors/therapeutic use , Norepinephrine/metabolism , Rats , Rats, Sprague-Dawley , Selegiline/therapeutic use
5.
Endocrine ; 10(3): 291-5, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10484293

ABSTRACT

Lipopolysaccharide (LPS) is known to produce several central and neuroendocrine effects and some of these effects are believed to be mediated through cytokines and other proteins. One such protein, leptin, produced by adipose tissue has been shown to cause anorexia, a central effect associated with LPS treatment. This raised the possibility that LPS-induced effects on feeding behavior may be mediated through leptin. This study was done to investigate the effects of systemic administration of LPS on plasma leptin levels in rats and the possible involvement of interleukin-1 (IL-1) in this mechanism. Adult male rats were implanted with indwelling jugular catheters and after collecting two pretreatment blood samples, the animals were injected (i.p.) with saline, 5 microg, 10 microg, or 25 microg/kg BW of LPS, or treated with 25 microg of soluble IL-1 receptor (sIL-1R) 5 min before and 90 min after 25 microg/kg BW of LPS. Posttreatment blood samples were collected at 30 min intervals for a period of 6 h. Plasma leptin concentrations were measured by radioimmunoassay. Treatment with saline did not produce any change in plasma leptin levels. In contrast, each of the three doses of LPS produced a dose-dependent increase in plasma leptin levels within 120 min. Leptin levels remained elevated for the next 4 h. Treatment with sIL-1 R completely blocked the LPS-induced increase in leptin levels, indicating that this effect is in fact mediated through IL-1. These results indicate that leptin could be a possible mediator of LPS-induced effects on feeding.


Subject(s)
Lipopolysaccharides/administration & dosage , Proteins/metabolism , Animals , Escherichia coli , Kinetics , Leptin , Male , Radioimmunoassay , Rats , Rats, Sprague-Dawley , Receptors, Interleukin-1/administration & dosage , Solubility
6.
Neurosci Lett ; 270(2): 79-82, 1999 Jul 30.
Article in English | MEDLINE | ID: mdl-10462102

ABSTRACT

In vivo release of catecholamines in the medial basal hypothalamus (MBH) by L-deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, was measured in young male Sprague-Dawley rats with stereotaxically implanted push-pull cannulae in the MBH and perfused with 0 (control), 1.5, 2.5 or 10.0 microg deprenyl in 20 microl of saline. Perfusate samples were collected at 20-min intervals and analyzed for norepinephrine (NE) and dopamine (DA) by high performance liquid chromatography (HPLC)-EC. NE release in the MBH was enhanced following perfusion with 2.5 and 10.0 microg deprenyl while DA release was augmented after infusion of 10.0 microg of deprenyl. There were no significant alterations in the release of NE and DA in the control and 1.5 microg deprenyl groups. These results suggest that deprenyl-induced in vivo release of catecholamines in the MBH may be involved in the reversal of some of the reproductive aging processes.


Subject(s)
Dopamine/metabolism , Hypothalamus, Middle/drug effects , Hypothalamus, Middle/metabolism , Monoamine Oxidase Inhibitors/pharmacology , Norepinephrine/metabolism , Selegiline/pharmacology , Animals , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Male , Rats , Rats, Sprague-Dawley
7.
Brain Res ; 824(2): 232-7, 1999 Apr 10.
Article in English | MEDLINE | ID: mdl-10196453

ABSTRACT

The purpose of this study was to examine the specificity in the effects of lipopolysaccharide (LPS) on monoamine concentrations in different areas of the brain and the involvement of interleukin-1 (IL-1) in the LPS-induced effects. Adult male rats were injected i.p. with saline, 10 micrograms/kg body weight of LPS, or treated with 250 micrograms of IL-1 receptor antagonist (IL-1ra) 5 min before and 2 h after LPS. Several brain areas including the hippocampus (HI), caudate putamen (CP), the hypothalamic paraventricular nucleus (PVN), arcuate nucleus (AN), median eminence (ME) and the medial preoptic area (MPA) were microdissected and analyzed for neurotransmitter concentrations by HPLC-EC. LPS treatment produced marked increases in the concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the PVN. In the AN, it increased DA concentrations and was without any effect on the MPA, ME, CP and HI. Treatment with IL-1ra in combination with LPS completely blocked the LPS-induced effects. It is concluded that LPS produces highly specific changes in monamine metabolism in the hypothalamus and that these effects are mediated at least in part by IL-1beta.


Subject(s)
Biogenic Monoamines/metabolism , Brain Mapping , Brain/drug effects , Lipopolysaccharides/pharmacology , Receptors, Interleukin-1/antagonists & inhibitors , Analysis of Variance , Animals , Brain/metabolism , Chromatography, High Pressure Liquid , Dissection , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Neurosecretory Systems/drug effects , Rats , Rats, Sprague-Dawley
8.
Endocrine ; 9(1): 33-7, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9798728

ABSTRACT

Serotonin is known to stimulate prolactin secretion by decreasing tyrosine hydroxylase (TH) activity in the tuberoinfundibular dopaminergic (TIDA) neurons. However, the effects of aging on the responsiveness of TIDA neurons to serotonin are not known. An effective way to increase serotonergic activity is to administer 5-hydroxytryptophan (5-HTP), a serotonin precursor. The present study was done to investigate the effects of 5-HTP on TIDA neuronal activity in aging animals. Middle-aged (10-12 mo), old (18-20 mo), and very old (22-24 mo) female Sprague-Dawley rats were bilaterally ovariectomized. Ten days later, they were injected iv with 50 mg/kg body wt of 5-HTP or the vehicle for 5-HTP (PBS-HCI). Twenty minutes later, m-hydroxybenzylhydrazine (NSD), a DOPA decarboxylase inhibitor, was administered. Ten minutes later, the animals were killed, and tyrosine hydroxylase (TH) activity was determined by measuring L-DOPA accumulation in the stalk median eminence by HPLC-EC. In all three groups, administration of 5-HTP increased serum prolactin levels significantly. In control middle-aged rats, TH activity (L-DOPA pg/ microg protein) was 33.0+/-5.6. Treatment with 5-HTP decreased TH activity by 60%. Similarly, 5-HTP treatment decreased TH activity by 52 and 56% in 18- to 20- and 22- to 24-mo-old rats, respectively, compared to the control rats. The magnitudes of the 5-HTP-induced decreases in TH activities in middle-aged, old, and very old rats were not different from each other. These results indicate that TIDA neuronal responsiveness to serotonin does not change with age and that 5-HTP is capable of stimulating PRL release even in very old rats.


Subject(s)
5-Hydroxytryptophan/pharmacology , Aging/physiology , Arcuate Nucleus of Hypothalamus/physiology , Neurons/drug effects , Neurons/physiology , Animals , Arcuate Nucleus of Hypothalamus/drug effects , Dopamine/physiology , Female , Ovariectomy , Protein Precursors/pharmacology , Rats , Rats, Sprague-Dawley , Serotonin/physiology
9.
Brain Res Bull ; 47(1): 29-34, 1998 Sep 01.
Article in English | MEDLINE | ID: mdl-9766386

ABSTRACT

The purpose of this study was to examine specificity in the effects of interleukin-1beta (IL-1beta) on monoamines in various areas of the hypothalamus. Adult male rats were injected i.p. with saline or 2.5 or 5.0 microg of IL-1beta or were pretreated with 500 microg of IL-1 receptor antagonist (IL-1ra) followed 5 min later by 5 microg of IL-1beta. The paraventricular nucleus (PVN), arcuate nucleus (AN), median eminence (ME), and medial preoptic area (MPA) were microdissected and analyzed for neurotransmitter concentrations by high-performance liquid chromatography with electrochemical detection (HPLC-EC). In the PVN, IL treatment produced significant increases in the concentrations of norepinephrine (NE), dopamine (DA), DA metabolite dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and its metabolite 5-hydroxyindoleacetic acid (5-HIAA). IL-1 treatment increased the concentrations of NE and DA in the AN but only of NE in the ME, and it was without any effect in the MPA. Pretreatment with IL-1ra completely blocked the IL-1 effects. It is concluded that IL-1 induces highly specific changes in monoamine metabolism in the hypothalamus, and the nature of these changes depends on specific hypothalamic nuclei.


Subject(s)
Biogenic Amines/metabolism , Hypothalamus/drug effects , Interleukin-1/pharmacology , Analysis of Variance , Animals , Arcuate Nucleus of Hypothalamus/drug effects , Chromatography, High Pressure Liquid , Electrochemistry , Hypothalamus/metabolism , Interleukin-1/antagonists & inhibitors , Male , Median Eminence/drug effects , Paraventricular Hypothalamic Nucleus/drug effects , Rats , Rats, Sprague-Dawley
10.
Proc Soc Exp Biol Med ; 217(4): 461-5, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9521094

ABSTRACT

Prolactin (PRL) secretion is under the inhibitory regulation of the tuberoinfundibular dopaminergic (TIDA) system. Short-term elevation in PRL levels has been shown to increase the activity of TIDA neurons, however, the responsiveness of TIDA neurons to chronically elevated serum PRL levels is controversial. The purpose of this study was to investigate the effects of prolonged elevations of serum PRL on TIDA neuronal activity. Female Sprague-Dawley rats (2-3 months old) were ovariectomized and implanted (s.c.) with haloperidol (HAL), a dopamine receptor antagonist for 6 or 9 months to produce hyperprolactinemia. Ovariectomized, sham-implanted rats were used as controls. Other groups of intact rats were implanted with HAL or sham-implanted for 9 months and then were implanted with PRL-producing MMQ cells for 6 weeks to further increase circulating PRL levels. TIDA neuronal activity was measured in terms of tyrosine hydroxylase (TH) activity in the stalk-median eminence and was correlated with changes in serum PRL levels. After 6 months of treatment, TH activity in HAL-treated rats was 130% higher than that in the control rats. After 9 months of treatment, TH activity in HAL-treated rats was 81% higher than that in control rats. This increase was significantly less than the increase that occurred after 6 months of treatment. Nine months of HAL-induced hyperprolactinemia followed by implantation of PRL-producing MMQ cells, which resulted in very high levels of PRL, did not increase TH activity in the stalk-median eminence. These results demonstrate that hyperprolactinemia over a prolonged period reduces the responsiveness of TIDA neurons, and these effects vary depending on the duration and intensity of hyperprolactinemia.


Subject(s)
Dopamine/physiology , Median Eminence/enzymology , Neurons/enzymology , Prolactin/blood , Tyrosine 3-Monooxygenase/metabolism , Animals , Arcuate Nucleus of Hypothalamus/physiology , Body Weight/drug effects , Dopamine Antagonists/pharmacology , Estrus , Female , Haloperidol/pharmacology , Hyperprolactinemia/metabolism , Organ Size/drug effects , Pituitary Gland/chemistry , Pituitary Gland/drug effects , Prolactin/analysis , Rats , Rats, Sprague-Dawley , Tumor Cells, Cultured
11.
Brain Res Bull ; 42(4): 265-71, 1997.
Article in English | MEDLINE | ID: mdl-9043712

ABSTRACT

HPLC and Palkovits' microdissection technique were used to measure activities of two catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH) and dopa decarboxylase (DD), in the medial preoptic area (MPA) and arcuate nucleus (AN), both of which are involved in LH regulation. The measurements were made during an 8-h period at 1200, 1400, 1600, 1800, and 2000 h on the days of proestrus and diestrus in young (4-5-month-old) rats. Similar measurements were made at 1400, 1600, 1800, and 2000 h in middle-aged (8-10-month-old) proestrous rats and in 18-22-month-old persistently diestrous rats. For each hour (1200, 1400, etc.), five to seven rats were used. In the young proestrous rats, TH activity in the MPA increased progressively to maximum levels at 1800 h, which is approximately the time when the proestrous surge of LH is known to occur. In contrast, in the young diestrous rats, in which serum LH is known to remain stable, TH activity remained unchanged throughout the afternoon. As in the young proestrous rats, in the middle-aged proestrous rats TH activity reached a peak at 1800 h followed by a precipitous decline at 2000 h. As in the young diestrous rats, in the old persistently diestrous rats no changes in TH activity were observed. The profiles of TH activity in the AN of the four groups were essentially similar to those in the MPA. The cyclic changes in TH activity observed in this study provide a basis for the reported cyclic changes in NE activity, which, in turn, are believed to be responsible for cyclic changes in LH release. The marked deficiency and absence of changes in TH activity in the acyclic old animals corresponded to the reported marked decrease and absence of fluctuations in catecholamine activity in old age. A correlation between DD activities and catecholamine activities was not obvious, most probably due to the large number of compounds that are known to be substrates for this enzyme.


Subject(s)
Aging/metabolism , Arcuate Nucleus of Hypothalamus/enzymology , Dopa Decarboxylase/metabolism , Preoptic Area/enzymology , Tyrosine 3-Monooxygenase/metabolism , Animals , Chromatography, High Pressure Liquid , Estrus/metabolism , Female , Rats , Rats, Sprague-Dawley
12.
Life Sci ; 61(18): 1783-8, 1997.
Article in English | MEDLINE | ID: mdl-9365225

ABSTRACT

The direct effects of deprenyl on the pituitary were investigated by measuring the release of luteinizing hormone (LH) from the pituitary glands of male Sprague-Dawley rats in vitro. Basal release of LH was determined by incubating the pituitaries in Krebs-Ringer Henseleit (KRH) solution with 0, 0.1, 1, or 10 mM of deprenyl for 1 h. In the control group, LH release was not different in pre- and posttreatment periods. In contrast, in the 10 mM group, LH release increased by 436% (p<0.01). Incubation of pituitaries with 0.1 or 1 mM deprenyl did not alter LH release. It is concluded that deprenyl a monoamine oxidase inhibitor, can also act directly on the pituitary.


Subject(s)
Luteinizing Hormone/metabolism , Monoamine Oxidase Inhibitors/pharmacology , Pituitary Gland/drug effects , Selegiline/pharmacology , Animals , In Vitro Techniques , Male , Pituitary Gland/metabolism , Radioimmunoassay , Rats , Rats, Sprague-Dawley
13.
Brain Res Bull ; 42(6): 435-41, 1997.
Article in English | MEDLINE | ID: mdl-9128918

ABSTRACT

The tuberoinfundibular dopaminergic (TIDA) system is known to inhibit prolactin (PRL) secretion. In young animals this system responds to acute elevations in serum PRL by increasing its activity. However, this responsiveness is lost in aging rats with chronically high serum PRL levels. The purpose of this study was to induce hyperprolactinemia in rats for extended periods of time and examine its effects on dopaminergic systems in the brain. Hyperprolactinemia was induced by treatment with haloperidol, a dopamine receptor antagonist, and Palkovits' microdissection technique in combination with high-performance liquid chromatography was used to measure neurotransmitter concentrations in several areas of the brain. After 6 months of hyperprolactinemia, dopamine (DA) concentrations in the median eminence (ME) increased by 84% over the control group. Nine months of hyperprolactinemia produced a 50% increase in DA concentrations in the ME over the control group. However, DA response was lost if a 9-month long haloperidol-induced hyperprolactinemia was followed by a 1 1/2 month-long extremely high increase in serum PRL levels produced by implantation of MMQ cells under the kidney capsule. There was no change in the levels of DA, norepinephrine (NE), serotonin (5-HT), or their metabolites in the arcuate nucleus (AN), medial preoptic area (MPA), caudate putamen (CP), substantia nigra (SN), and zona incerta (ZI), except for a decrease in 5-hydroxyindoleacetic acid (5-HIAA) in the AN after 6-months of hyperprolactinemia and an increase in DA concentrations in the AN after 9-months of hyperprolactinemia. These results demonstrate that hyperprolactinemia specifically affects TIDA neurons and these effects vary, depending on the duration and intensity of hyperprolactinemia. The age-related decrease in hypothalamic dopamine function may be associated with increases in PRL secretion.


Subject(s)
Dopamine/metabolism , Hyperprolactinemia/metabolism , Neurons/metabolism , Age Factors , Animals , Body Weight/drug effects , Cells, Cultured , Female , Rats , Rats, Sprague-Dawley , Time Factors
14.
Brain Res ; 689(1): 122-8, 1995 Aug 14.
Article in English | MEDLINE | ID: mdl-8528695

ABSTRACT

Push-pull perfusion and HPLC were used to measure the release of norepinephrine (NE) and dopamine (DA) in the medial basal hypothalamus of young (4-5 months old), middle-aged (8-10 months old), and old (22-24 months old) rats. In the young animals, the afternoon of proestrus was characterized by a gradual increase in NE release and a simultaneous gradual decrease in DA release. The peak in NE release and the nadir in DA release occurred at about the time when the proestrous surges in serum LH and PRL are known to occur. No changes in NE and DA releases occurred in the afternoon of diestrus when serum LH and PRL are known to remain stable. In the middle-aged proestrous animals, the patterns of NE and DA releases were similar to those in the young proestrous animals, but the peak in NE release was attenuated and did not reach statistical significance. This corresponded with the reported attenuation in the LH surge in middle age. In the old persistently diestrous animals, NE and DA were released at constant rates, which correlated with the well-documented constant levels of serum LH and PRL in old age. These data provide an explanation for the simultaneous proestrous surges of LH and PRL and lead us to conclude that NE plays a facilitatory role in the LH surge, while DA, through its inhibitory action, regulates the PRL surge.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Aging/metabolism , Dopamine/metabolism , Hypothalamus, Middle/metabolism , Norepinephrine/metabolism , Periodicity , Analysis of Variance , Animals , Catheterization , Chromatography, High Pressure Liquid , Electrochemistry , Female , Perfusion , Rats , Rats, Sprague-Dawley
15.
Endocrinology ; 136(3): 1103-10, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7867565

ABSTRACT

The purpose of this study was to investigate the effects of long term treatment with deprenyl, a monoamine oxidase-B inhibitor, on estrous cyclicity, serum PRL, incidence of mammary and pituitary tumors, and monoamine metabolism in the medial basal hypothalamus (MBH) and striatum (ST) of old female rats. Acyclic female Sprague-Dawley rats (15-16 months old) were treated sc with 0, 0.25, or 2.5 mg deprenyl/kg BW.day for more than 8 months. Body weight and food intake were measured every week, and the estrous cycles and development of mammary tumors were monitored throughout the treatment period. At the end of the treatment period, the concentrations of catecholamines, serotonin, and their metabolites in the MBH and ST were determined by HPLC with electrochemical detection. The wet weights of the pituitary, heart, liver, lung, kidney, adrenals, uterus, and ovaries were recorded. Trunk blood was collected for measurement of serum PRL concentrations by RIA. Deprenyl treatment temporarily reestablished estrous cycles in most of the rats. The incidence of pituitary and mammary tumors was markedly reduced in the deprenyl-treated rats compared with that in the saline-treated control rats. Deprenyl had no significant effect on the weights of internal organs. The high dose of deprenyl (2.5 mg/kg) decreased serum PRL concentrations significantly. There were no significant differences in body weight or food intake between the control and deprenyl-treated groups. Deprenyl decreased the concentrations of the monoamine metabolites, dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid, in both the MBH and ST. It had no effect on the concentrations of norepinephrine and dopamine in the MBH, but significantly increased norepinephrine concentrations in the ST and serotonin concentrations in both the MBH and ST (P < 0.05). It is concluded that deprenyl treatment exerted these effects via suppression of monoamine metabolism.


Subject(s)
Aging/physiology , Estrus/drug effects , Mammary Neoplasms, Experimental/prevention & control , Pituitary Neoplasms/prevention & control , Prolactin/blood , Selegiline/pharmacology , Animals , Body Weight/drug effects , Female , Menopause , Organ Size/drug effects , Rats , Rats, Sprague-Dawley
16.
Brain Res Bull ; 38(6): 561-4, 1995.
Article in English | MEDLINE | ID: mdl-8590078

ABSTRACT

High-performance liquid chromatography with electrochemical detection (HPLC-EC) and Palkovits' microdissection technique were used to measure norepinephrine (NE) concentrations in the medial preoptic area (MPA) and arcuate nucleus (AN) during various stages of the estrous cycle. NE was measured seven times at 2-h intervals between 1000 h and 2200 h on the days of proestrus and diestrus in young (4-month-old) rats and four times at 2-h intervals between 1400 h and 2000 h in old (20-22-month-old) persistently diestrous rats. On the day of proestrus in young animals, NE increased progressively from low levels at 1000 h to peak levels at 2000 h, followed by a sharp decline at 2200 h. In contrast, no changes in NE occurred on the day of diestrus. Unlike the young proestrous rats, but similar to the young diestrous rats, no changes in NE concentrations either in the MPA or in the AN occurred in the old persistently diestrous rats. These data demonstrate that NE concentrations in the MPA and AN change during the estrous cycle. We believe the increase in NE on the afternoon of proestrus is related to the surge in serum luteinizing hormone (LH) that occurs simultaneously in this stage of the estrous cycle. The lack of change in NE concentrations in the young diestrous and persistently diestrous old animals is consistent with the well-established absence of changes in serum LH in these animals.


Subject(s)
Arcuate Nucleus of Hypothalamus/metabolism , Norepinephrine/analysis , Preoptic Area/metabolism , Age Factors , Animals , Estrus/physiology , Female , Norepinephrine/physiology , Rats , Rats, Sprague-Dawley
17.
Endocrinology ; 135(1): 119-26, 1994 Jul.
Article in English | MEDLINE | ID: mdl-8013343

ABSTRACT

The roles of hypothalamic norepinephrine (NE) and dopamine (DA) in the regulation of LH and PRL are controversial. In the present studies, we used HPLC and push-pull perfusion to measure NE and DA releases in the medial preoptic area (MPA) of conscious, freely moving rats. Serum LH and PRL were determined in separate groups of rats with indwelling venous cannulas. In young (4- to 5-month-old) rats, concomitant with proestrous surges of serum LH and PRL, NE release in the MPA increased gradually to reach a peak at 1800 h, whereas DA release decreased gradually to its lowest level at 2000 h. Compared to the young animals, in middle-aged (8- to 10-month-old) animals, the proestrous surge of PRL was unaltered, but the LH surge was delayed and attenuated. The pattern of DA release in the middle-aged animals was also unaltered, but the peak in NE release was markedly attenuated, although the average NE release was increased compared to that in the young proestrous animals. In young diestrous rats and old (22- to 24-month-old), persistently diestrous rats, in which serum LH and PRL are known to be stable, both NE and DA releases were devoid of fluctuations. However, in the young diestrous animals, the average NE and DA releases were significantly increased compared to those in the young proestrous animals, whereas in the old, persistently diestrous animals, NE and DA releases were markedly reduced compared to those in the young diestrous animals. These data lead us to conclude that NE, through its stimulatory action, may be the primary regulator of LH release, and that it is the pattern, rather than the level, of NE release that appears to be critical in determining the pattern of LH release. DA, through its inhibitory action, appears to control PRL only and probably has no association with LH release. By tracing NE and DA activities from adulthood through middle-age to senescence, these studies revealed that the marked reductions in catecholamines in old age are preceded by a transitory increase in NE activity in middle-age, and that the cyclic increase in NE activity associated with the LH surge begins to diminish in middle age and disappears completely in old age.


Subject(s)
Aging/blood , Catecholamines/metabolism , Luteinizing Hormone/blood , Preoptic Area/metabolism , Proestrus , Prolactin/blood , Animals , Chromatography, High Pressure Liquid , Dopamine/blood , Female , Norepinephrine/blood , Perfusion/methods , Rats , Rats, Sprague-Dawley
18.
Life Sci ; 54(13): 841-5, 1994.
Article in English | MEDLINE | ID: mdl-8139373

ABSTRACT

The effects of i.v. administration of deprenyl (2.5, 5, and 10.0 mg/Kg body wt), a monoamine oxidase inhibitor, on serum prolactin (PRL) concentrations were investigated in female Sprague-Dawley rats. In the rats treated with the highest dose (10 mg/Kg), serum PRL decreased by 48% (p < 0.05) within 30 min and remained depressed during a 240-min period. Serum PRL concentrations also decreased by 38% (p < 0.05) within 30 min in the rats treated with the 5 mg dose and remained low during the remainder of the period of observation. Serum PRL levels showed no change in the group treated with 2.5 mg of deprenyl/Kg BW, except at 240 min when it was 48% (p < 0.05) below the pretreatment levels. In the control group, injected with the vehicle (0.5 ml saline) no decreases in PRL levels were observed. The average serum PRL concentrations during the entire posttreatment period were 45% above the pretreatment levels in the control group, whereas they were 31% and 43% below the respective pretreatment levels in the 5 and 10 mg groups, respectively. In the 2.5 mg group, the average serum PRL levels during the posttreatment period were not different from those in the pretreatment period. It is concluded that deprenyl is a potent inhibitor of PRL release in the rat.


Subject(s)
Prolactin/blood , Selegiline/pharmacology , Animals , Dose-Response Relationship, Drug , Female , Monoamine Oxidase Inhibitors/pharmacology , Prolactin/metabolism , Rats , Rats, Sprague-Dawley
19.
Proc Soc Exp Biol Med ; 203(2): 236-42, 1993 Jun.
Article in English | MEDLINE | ID: mdl-7684845

ABSTRACT

The purpose of this study was to investigate the mechanism by which underfeeding induces regression of carcinogen-induced mammary tumors in the rat and to determine if tumor regression in underfed rats could be prevented on a chronic basis by maintaining elevated circulating levels of estrogen and/or prolactin (PRL) by treatment with estradiol benzoate (EB) and a dopamine receptor blocker, haloperidol (HAL). Female rats with 7,12-dimethylbenzanthracene-induced mammary tumors were fed ad libitum (full-fed), half-fed (HF), or half-fed and treated wtih EB (HF+EB), HAL (HF+HAL), or both (HF+EB+HAL) for 15 weeks. Tumor diameter, tumor number, and body weight were determined each week. At the end of the experiment, hypothalamic concentrations of catecholamines, indoleamines, and their metabolites were determined by high performance liquid chromatography. Tumor diameter, tumor number, and body weight increased progressively in the full-fed rats, but decreased significantly in the HF rats. Treatment of HF rats with EB, HAL, or both prevented tumor regression, but had no effect on body weight, which declined continuously. In the HF rats, there was an increase in the concentration of dopamine and a decrease in the concentration of serotonin in the hypothalamus, whereas treatment with HAL reversed these effects. EB had no effect on neurotransmitter concentrations in the HF rats, but treatment of HF+EB animals with HAL decreased the dopamine concentration. The changes in dopamine and serotonin observed in HF rats are known to inhibit PRL secretion, whereas HAL, which blocked these changes, is a well established stimulator of PRL secretion. Since the mammary tumors are dependent on PRL for development and growth, it is probable that the regression of these tumors in the HF rats was ultimately due to a decrease in PRL secretion, and the prevention of this regression in HF+HAL rats was ultimately due to an increase in PRL secretion. EB, a potent PRL stimulator, probably blocked tumor regression in HF+EB rats by increasing PRL secretion by a direct effect on the pituitary.


Subject(s)
Estradiol/pharmacology , Food Deprivation , Haloperidol/pharmacology , Mammary Neoplasms, Experimental/therapy , 9,10-Dimethyl-1,2-benzanthracene , Animals , Body Weight , Dopamine/metabolism , Female , Hydroxyindoleacetic Acid/metabolism , Hypothalamus/drug effects , Hypothalamus/metabolism , Mammary Neoplasms, Experimental/chemically induced , Mammary Neoplasms, Experimental/pathology , Prolactin/metabolism , Rats , Rats, Sprague-Dawley , Serotonin/metabolism
20.
Life Sci ; 52(24): 1961-7, 1993.
Article in English | MEDLINE | ID: mdl-8505861

ABSTRACT

The purpose of this study was to investigate the effects of circulating interleukin-1 beta (IL-1 beta) on the release of norepinephrine (NE) in the paraventricular nucleus (PVN). After intraperitoneal administration of IL-1 beta, NE was measured by high performance liquid chromatography in the perfusate collected from the PVN of conscious, freely moving rats by the technique of push-pull perfusion. IL-1 beta produced an increase in NE release. Both the strength and duration of NE release were dose-dependent. It is concluded that circulating IL-1 beta activates the noradrenergic innervation to the PVN and that this is part of the mechanism by which it stimulates the release of the corticotropin-releasing hormone (CRH) and produces its other neuroendocrine and central effects.


Subject(s)
Interleukin-1/pharmacology , Norepinephrine/metabolism , Paraventricular Hypothalamic Nucleus/physiology , Animals , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Humans , Interleukin-1/administration & dosage , Male , Paraventricular Hypothalamic Nucleus/drug effects , Perfusion , Rats , Rats, Sprague-Dawley , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology , Reference Values , Stereotaxic Techniques
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