Distribution of zinc in the substantia nigra of rats treated with 6-hydroxydopamine

To study the relationship between tissue accumulation of Zinc (Zn) and neurodegeneration in the nigrostriatal dopaminergic pathway,⁶⁵Zn distribution in this pathway was examined after unilateral injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra of rats. When⁶⁵ZnCl₂ was intravenously injected 4 days after treatment with 6-OHDA,⁶⁵Zn was concentrated in the ipsilateral substantia nigra 6 days after⁶⁵Zn injection. On the other hand, 19 d after treatment with 6-OHDA,⁶⁵Zn distribution in the ipsilateral substantia nigra was decreased to the level of the contralateral one. When NH₄ ⁹⁹TcO₄, which cannot go through the blood-brain barrier, was injected into rats 4 d after treatment with 6-OHDA,⁹⁹Tc was concentrated in the ipsilateral substantia nigra 30 min after⁹⁹Tc injection, but no longer detectable 6 d after injection. These results suggest that Zn is necessary for a repair process called replacement gliosis after the death of neurons and that excess Zn does not accumulate in the lesion after completion of the gliosis.     

The effect of 6-hydroxydopamine on the behavior of rats with differing resistance to stress exposure

The influences of 6-OHDA (150 mcg intraventricular, bilaterally) on the behaviour of Wistar rats with different resistance to sound-stress were studied. Reduction of reactivity, exploratory activity and learning deterioration after 6-OHDA administration were observed. The behavioural disturbances were more demonstrative in stress-resistant rats. Biochemical estimations showed that 6-OHDA induced a reduction of brain noradrenaline level in stress-resistant rats and a reduction of dopamine level in nonresistant animal. It is suggested that more demonstrative behavioural disturbances induced by 6-OHDA in stress-resistant rats are connected with deficit of brain noradrenaline.     

The effect of chronic estrogen treatment on immunoreactive beta-endorphin levels in intact female rats

Intact female rats were treated chronically with estradiol benzoate (EB) until a state of constant estrus (CE) was achieved and maintained. When compared to female rats on the day of estrus, estrogen-treated rats in constant estrus demonstrated a 33% decrease in the concentration of immunoreactive beta-endorphin (IR-BE) in the plasma, and a 45-50% decrease in the content and concentration of IR-BE in the anterior pituitary and hypothalamus. The content and concentration of IR-BE in the neurointermediate lobe of the pituitary were similar in each group. Column chromatography revealed that the reduction in IR-BE in the plasma and anterior pituitary of EB-treated CE female rats appeared to be due to a reduction in peptides coeluting with beta-endorphin and beta-lipotropin, whereas the reduction in IR-BE in the hypothalamus represented a decrease in a peptide which coeluted with beta-endorphin. These data suggest that constant estrus, induced by prolonged treatment of intact female rats with estrogen, resulted in a reduction in central and peripheral levels of IR-BE in these animals as compared to female rats on the day of estrus.     

Evidence that physiological levels of circulating leptin exert a stimulatory effect on luteinizing hormone and prolactin surges in rats.

Increasing evidence suggests that leptin, an adipocyte-derived hormone, may positively regulate the reproductive axis, and serve as a critical metabolic signal linking nutrition and the reproductive function. However, along this line there remains an as-of-yet unresolved important issue whether physiological levels of circulating leptin exert a stimulatory effect on the reproductive axis. It is also unknown whether hyperleptinemia affects the reproductive function. In this study, we attempted to examine these unexplored issues, employing as an indicator the estradiol/progesterone-induced luteinizing hormone (LH) and prolactin (PRL) surges in ovariectomized female rats. Experiments were performed on normally fed, 3-day starved, 3-day starved + murine leptin (100 microg/kg/day), and normally fed + murine leptin (300 microg/kg/day) groups. Leptin was administered utilizing osmotic minipumps during 3 days immediately before experimentation. From 11:00 to 18:00 h, blood was collected every 30 min to measure LH and PRL. The 3-day starvation completely abolished both LH and PRL surges, but 3-day starved + leptin (100 microg/kg/day) group, whose plasma leptin levels (3.7 +/- 0.4 ng/ml) were similar to those in normally fed group (3.4 +/- 0.5 ng/ml), showed a significant recovery of the hormonal surges. On the other hand, the magnitudes of LH and PRL surges in normally fed + leptin (300 microg/kg/day) group, whose leptin levels were 10.8 +/- 1.5 ng/ml, were statistically the same as those in normally fed group. These results indicate for the first time that physiological concentrations of circulating leptin exert a stimulatory effect on the steroid-induced LH and PRL surges in the rat. It was also suggested that mild hyperleptinemia of 3 days' duration may not significantly affect the hormonal surges.     

The effect of feeding on plasma immunoreactive ACTH and beta-endorphin levels in newborn infant.

In order to clarify whether an interaction between endogenous opioids and feeding occurs at birth, we studied Beta-endorphin (beta-EP) and ACTH plasma levels in response to a feed of 10% glucose, or formula, in 120 healthy full-term infants. Neither postprandial beta-EP nor ACTH increases were found at the 24th hour or on the fourth day of life. beta-EP physiology in newborn infants seems to be different from adults.     

The influence of long-term estrogen treatments on daily plasma prolactin levels in ovariectomized rats

Prolactin levels were determined in the plasma of female rats from 4 to 54 days after ovariectomy or ovariectomy and treatment with a long acting polymer of estradiol, polyestradiol phosphate (PEP), or Silastic implants of crystalline estradiol-17β. Blood samples were withdrawn from indwelling aortic catheters in the morning (0900–1100) and afternoon (1500–1700). Both methods of estrogen delivery elevated plasma prolactin in the morning and afternoon compared to ovariectomized controls. However, the increases in the afternoon were significantly greater than those in the morning. The difference from ovariectomized controls and the morning-afternoon differences were maintained for 25–26 days in the polyestradiol phosphate-treated group whereas those differences in the group receiving the implants of estradiol were significant for the entire length of the experiment (54 days). In addition, there were periodic fluctuations in the morning and afternoon levels of prolactin in the estradiol implanted animals. It is suggested that the plasma prolactin response to estrogen varies with time of day, time after administration of estrogen and with the method of estrogen delivery.     

Novel 8 alpha-ergolines with inhibitory and stimulatory effects on prolactin secretion in rats

Four derivatives of the ergot dopamine (DA) agonist lisuride (LIS), namely 6-n-propyl-lisuride (6-n-propyl-LIS), transdihydrolisuride (TDHL), 6-n-propyl-transdi-hydrolisuride (6-n-propyl-TDHL) and 2-bromolisuride (2-Br-LIS) were investigated in female rats with regard to their influence on hyperprolactinaemia induced by pretreatment with reserpine (2 mg/kg i.p., 24 h) at various intervals following their subcutaneous or oral administration (0.05 mg/kg). Two hours after administration, LIS, 6-n-propyl-LIS, and 6-n-propyl-TDHL caused a statistically significant inhibition of reserpine-induced hyperprolactinaemia of about the same extent. Eight hours after administration 6-n-propyl-LIS and 6-n-propyl-TDHL were as active as after 2 h in inhibiting prolactin (PRL) secretion whereas LIS was almost ineffective in this respect. TDHL caused a statistically significant inhibition of PRL secretion at 2 and 8 h after oral administration; this effect was less pronounced after s.c. administration. In contrast to the aforementioned derivatives 2-Br-LIS further increased the reserpine-induced hyperprolactinaemia. In normal male rats pretreatment with 2-Br-LIS (0.025-6.25 mg/kg s.c., 2 h) dose-dependently stimulated PRL secretion. The present data support the assumption of the longlasting DA agonistic action of 6-n-propyl-LIS and 6-n-propyl-TDHL and of the antidopaminergic properties of 2-Br-LIS recently derived from behavioural studies.     

The influence of oral corticosterone replacement on plasma prolactin levels of adrenalectomized female rats

The administration of 80 μg of corticosterone/ml of drinking solution to adrenalectomized (ADX) rats resulted in a 24 hour serum corticosterone pattern similar to that of intact animals except that the magnitude of the afternoon-nocturnal surge was one third. Basal plasma prolactin levels and the estrogen-induced afternoon prolactin surge were similar for intact and for ADX animals receiving corticosterone in the drinking solution. Adrenalectomized animals receiving 0.9% NaCl to drink, however, had an afternoon prolactin surge that was significantly lower than that of intact animals while basal levels were similar.     

Effects of serotonergic agents on plasma prolactin levels in pyridoxine-deficient adult male rats

Plasma concentration of prolactin was significantly reduced in pyridoxine-deficient as compared to control (pyridoxine-supplemented) adult male rats. Administration of pyridoxine to deficient rats resulted in a significant increase in plasma prolactin. The reduction in plasma prolactin in pyridoxine-deficient rats corresponded with the significantly reduced hypothalamic contents of pyridoxal phosphate and serotonin in pyridoxine-deficient rats. Plasma prolactin concentrations were also measured in response to serotonergic agents in both groups of rats. The administration of the 5HT_1A agonist (8-hydroxy 2-n-dipropylamino tetralin) resulted in a significant increase in plasma prolactin and that of the specific 5HT_1A antagonist spiroxatrine had the opposite effect. The results suggest that the hypothalamic serotonergic regulation of prolactin release is impaired in pyridoxine deficiency.     

Effects of beta-endorphin fragments on plasma levels of vasopressin

Plasma vasopressin levels are significantly decreased after intracerebroventricular (icv) administration of β-endorphin (βE), but not of des-tyrosine βE (DTβE). The βE induced decrease of vasopressin levels, which occurs in normal as well as in water deprivated rats, can partially be blocked by naltrexone. γ-Endorphin (γE), α-endorphin (αE), DTγE and DTαE did not affect basal levels of vasopressin, but γE and DTγE further increased the elevated vasopressin levels in water deprivated rats. Naltrexone antagonized this increase following γE administration, but not that induced by DTγE. The results suggest that the effects of βE and its fragments on plasma vasopressin levels are mediated by multiple opiate and non-opiate receptor systems.     

A stimulatory effect by nerve growth factor on the regrowth of adrenergic nerve fibres in the mouse peripheral tissues after chemical sympathectomy with 6-hydroxydopamine

Summary Systemically administered Nerve Growth Factor (NGF) had a strong stimulating effect on the regeneration of fully developed adrenergic neurons in the peripheral tissues of the mouse after axotomy induced by 6-hydroxydopamine. The NGF stimulation was investigated at 9 and 21 days after the 6-hydroxydopamine injection, and was observed fluorescence histochemically as an increase in number, length, and thickness of the outgrowing adrenergic fibre bundles, in the extent and abundance of the terminal ramifications of the regrowing fibres, and in their fluorescence intensity. This increase in the regrowth of the lesioned adrenergic axons was paralleled by strong and significant increases in the recovery of endogenous noradrenaline in several peripheral tissues. The present findings demonstrate a sensitivity of fully developed adrenergic neurons to NGF during axonal regeneration, and it is suggested that NGF might play a normal physiological role in this process.     

Effects of arginine vasotocin on levels of plasma gonadotropins and prolactin in ovariectomized conscious rats

Arginine vasotocin was injected into the third ventricle or intravenously in conscious, ovariectomized rats and its effect on gonadotropin and prolactin release evaluated. The peptide lowered plasma levels of both LH and prolactin in doses of 40 or 100 ng given intraventricularly. The higher dose was slightly more effective than the lower dose. Intravenous injection of a 1-microgram dose of vasotocin failed to alter plasma LH in the ovariectomized animals; however, a 5-micrograms dose induced a slight depression apparent at only 60 min following injection. Intravenous injection of 1 microgram produced a significant lowering of plasma prolactin, whereas a dramatic lowering followed the injection of the higher dose. Plasma FSH was unaffected in these experiments. Incubation of dispersed anterior pituitary cells from ovariectomized rats with various doses of vasotocin revealed no effect of the peptide on the release of FSH, LH, or prolactin. It also did not alter the response to LHRH, but it partially blocked the action of dopamine to inhibit prolactin release. The data indicate that quite low doses of arginine vasotocin act within the brain to inhibit LH and prolactin secretion in ovariectomized, conscious animals.     

The effect of glucocorticoids on plasma fibronectin levels in normal and arthritic rats

In vivo studies with normal and adjuvant-induced arthritic rats were undertaken in order to measure the effects of glucocorticoids on paw inflammation and plasma fibronectin (Fn) levels. Dexamethasone, methylprednisolone, and corticosterone all enhanced plasma Fn levels in normal animals. All drugs also significantly decreased inflammation in arthritic rats as measured by paw swelling. Of the three glucocorticoids, only corticosterone did not significantly enhance Fn levels in arthritic rats, possibly due to its lesser potency and narrow therapeutic window.     

The effect of high-fat diet on plasma ghrelin and leptin levels in rats

Ghrelin and leptin regulate appetite and energy homeostasis in humans and rodents. The effects of different nutritional factors on ghrelin and leptin secretion are not well documented in rats. Therefore, the aim of our study was to investigate the effect of a high-fat diet on plasma ghrelin and leptin levels and on adiposity. Twenty male Wistar rats, body weight220–260 g, were used in the study. Rats were randomized either on a standard chow diet (n=10) or on a high-fat diet (a mixture of nuts) forad libitum 11-week period. Body weight was measured once per week. At the end of the nutritional period, rats were sacrificed. Blood was collected for determination of lipids and glucose, as well as plasma ghrelin and leptin levels by ELISA method. The weight of different organs was determined. Rats fed on a high-fat diet showed significant increase in total body weight compared to control group. The long-term intake of high-fat diet caused hyperleptinemia and hypoghrelinemia. There was a significant positive correlation between plasma leptin levels and epididymal fat mass, liver and heart. In contrast, ghrelin levels showed inverse correlation with epididymal fat mass and liver weight. In conclusion, long-term intake of high-fat diet induced changes in plasma ghrelin and leptin in male rats, as well as in epididymal fat mass, liver and heart weights.     

Factors modifying the effect of diazepam on plasma corticosterone levels in rats

We have examined factors that alter the effect of diazepam (DZ) on plasma corticosterone (CS) in rats. DZ had a biphasic effect on plasma CS levels: CS decreased with doses below 5 mg/kg and increased with higher doses. Peak response occurred 90 minutes post injection in both sexes. Plasma DZ levels were significantly higher in females than in males and peak at 10 and 30 minutes post injection in males and females, respectively. There was also a sex difference in the pattern of DZ metabolites. An acute stressor (30 minutes of immobilization) did not affect plasma CS levels in rats injected with a 5 mg/kg dose of DZ. Prenatally stressed animals did not differ in basal CS levels or in their response to 5 mg/kg of DZ compared to prenatally non-stressed animals. These two groups of animals also did not differ in plasma levels of DZ or of its metabolites. By contrast, the 5 mg/kg dose of DZ had no effect on plasma testosterone levels in control animals, but increased it in prenatally stressed animals. Furthermore, compared to non-stressed controls, prenatally stressed animals had lower baseline plasma testosterone levels. These results indicate that the effect of DZ on plasma CS is influenced by endogenous as well as exogenous factors and that these effects vary with the particular biochemical parameter under examination.     

Differential effect of aging on serum levels of prolactin and alpha-melanotropin in rats.

Prolactin (PRL) and alpha-melanocyte-stimulating hormone (alpha-MSH) are the only two pituitary hormones whose basal secretion is under tonic dopaminergic inhibition exerted by the hypothalamus. In the female rat, continuous exposure to estrogens is believed to depress hypothalamic dopaminergic activity and lead to the appearance of PRL-secreting pituitary adenomas during aging. Since there is no information about the impact of aging on circulating alpha-MSH levels, it was of interest to assess and compare the serum levels of PRL and alpha-MSH in male and female rats of different ages. Young (3-4 months) and old (24-25 months) male and female Sprague-Dawley rats as well as senescent (33-35 months) females were killed by decapitation between 10 AM and 1 PM, and pituitaries were immediately removed and dissected. Hormones were measured in unextracted trunk serum by radioimmunoassay. Serum PRL levels were (mean +/- SE), 18.4 +/- 2.0, 26.8 +/- 3.8, 19.8 +/- 2.5, 43.0 +/- 7.5, and 193.5 +/- 47.6 ng/ml for young and old males, and young, old, and senescent females, respectively. Serum alpha-MSH levels were 243.2 +/- 15.2, 252.9 +/- 24.8, 320.0 +/- 31.3, 234.7 +/- 19.1, and 374.0 +/- 29.7 pg/ml for young and old males, and young, old and senescent females, respectively. Anterior pituitary and neurointermediate lobe weights increased significantly with age in both sexes, although the change was particularly conspicuous in the females. We conclude that aging does not have a major impact on circulating alpha-MSH levels in rats and that melanotrophs probably have a greater ability than prolactotrophs to withstand age-associated alterations in central regulatory mechanisms.