Hypothalamic histamine release in normal and stressed rats is affected by sex and aging.

Changes in the baseline and in the 40 mM K+-evoked release of histamine from hypothalamus slices were compared in male and female rats aged 2, 6, 12, 18, and 24 months. The baseline release declined in the 12-, 18-, and 24-month males. In contrast, the K+-evoked release remained constant in the males, but in the females it decreased in animals more than 2 months old. The efficiency of the H3 receptors was also determined by measuring the reduction of the K+-evoked release induced by the H3 receptor agonist (R)-alpha-methylhistamine. This substance significantly decreased the amount of HA released in all age groups, except the 24-month-old males. Histamine release was also measured after exposure to a weak electrical stress. In 2- and 6-month-old males, there was a marked reduction of both the baseline and the K+-evoked release, and also of the inhibitory effect of the H3 agonist. There were no changes in the 12- and 18-month age groups, but both releases were enhanced in the 24-month group. In females, electrical stress had no significant effect, except in the youngest age group. Stress-dependent release of plasma corticosterone was decreased in males older than 12 months and in females older than 6 months. These changes gave a good correlation with variation in the H3 receptors. This study, therefore, demonstrates that aging modifies, in a sex-dependent way, the basal and stress-stimulated functions of the hypothalamic presynaptic histaminergic neurons.

N-Acetyltransferase mechanism for alpha-melanocyte stimulating hormone regulation in rat ageing.

alpha-Melanocyte stimulating hormone (alpha-MSH) is a proopiomelanocortin-derived peptide involved in such behavioural activities as arousal, grooming, memory, learning and attention. Because of these effects, alpha-MSH can be considered the 'adaptation neuropeptide'. Two alpha-MSH major forms were described: acetyl alpha-MSH and des-acetyl alpha-MSH. Since the acetylated form of alpha-MSH is biologically significantly more effective than des-acetyl alpha-MSH, we studied the activity of N-acetyltransferase, the enzyme responsible for MSH acetylation, during ageing in rat hippocampus and pituitary. We observed a substantial decrease of enzyme activity during lifetime, suggesting that the lower synthesis of the more efficient acetylated alpha-MSH form can be related to the reduced adaptive capabilities of aged subjects.

Stress-induced changes in histaminergic system: effects of diazepam and amitriptyline.

The involvement of the histaminergic system in the regulation of weak stress was studied in rats. The parameters examined were the brain receptors and corticosterone (CS) plasma levels. The benzodiazepine diazepam [(2 mg/kg intraperitoneally (IP)] influenced neither foot-shock-induced changes in CS levels nor [3H]-histamine [(3H)-HA] binding site constants, whereas the tricyclic antidepressive amitriptyline (10 mg/kg IP) partially counteracted a plasma CS increase and prevented changes in [3H]-HA binding in the stressed rat brain. These observations are in agreement with the known activities of amitriptyline on monoaminergic metabolism and receptors. Moreover, these data provide further experimental evidence of the functional role of the central histaminergic system in organized stress response.

Stress and brain histaminergic system: effects of weak electric foot-shock.

A weak electric foot-shock stressful stimulus (0.5 mA x 1 s x 5 times) significantly increases plasma corticosterone (CS) levels and modifies [3H]-histamine ([3H]-HA) binding site constants related to H2 receptors in rat cortical membranes. Progressive and total recovery of basal binding characteristics occurs 90 min later. A double-foot-shock stress procedure delays [3H]-HA binding characteristic recovery instead of strengthening stress effects. This finding is further evidence of involvement of the brain's histamine receptors in the response to mild stress.

Sexual dimorphism in [3H]histamine binding sites of rat cerebral cortex.

[3H]Histamine binding sites, identified on rat brain homogenate membranes, displayed sexual dimorphism with higher density and lower affinity in preparations from adult female compared to the males. The ontogenetic development of [3H]histamine binding sites was studied in male and female brain cortex neural membranes. Histamine binding sites were detectable in newborn-10 day old rats. Density increased with age, reaching adult levels at 37-45 days. No significant differences between sexes were observed in the binding constants until 37 days after birth, when the [3H]histamine binding characteristics began to differentiate according to sex. Sexual dimorphism in brain histamine binding site development appeared to depend on ovarian steroids. Binding patterns in immature female rats which were ovariectomized at 21 days and killed at 37+ were similar to those found in males. On the other hand, when oestradiol replacement was administered for 10 days to ovariectomized rats a total recovery of [3H]histamine binding pattern was obtained, which was comparable to that observed in intact female rats of the same age.

Effects of chronic ethanol treatment on alpha-MSH concentrations in rat brain and pituitary.

Male Sprague-Dawley rats were chronically treated with a liquid diet containing 6.5% (v/v) ethanol or equicaloric sucrose. Rats were killed after 21 days of treatment. alpha-MSH-like immunoreactivity was measured in the intermediate lobe of the pituitary gland and in several brain regions. Chronic ethanol treatment significantly reduced alpha-MSH-like immunoreactivity in the pituitary gland; in the arcuate nucleus of the hypothalamus and in the substantia nigra. The results of this study confirm the earlier findings that chronic ethanol treatment reduces POMC biosynthesis in the pituitary gland and in the central nervous system.

Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors.

UNLABELLED: We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modifications induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17 beta-estradiol (E2) at both low (0.1 micrograms/kg) and high (20 micrograms/kg) doses confirmed its ability to increase the number of striatal 3H-Spiperone (3H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E2, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophyseal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. IN CONCLUSION: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of its antiestrogenic activity.

Biogenic amines in cerebrospinal fluid and plasma of patients with dementia of Alzheimer type.

The involvement of monoaminergic neurons in Dementia of Alzheimer Type (D.A.T.) is still a matter for debate. In a selected group of patients with D.A.T. we evaluated monoamine levels in cerebrospinal fluid (CSF) and plasma and found a significant decrease in serotonin and dopamine metebolite levels. Dopamine levels were reduced in both CSF and plasma. Moreover, a significant correlation was found between the duration of the illness and the decrease in monoamine levels. These findings suggest that there is systemic damage to monoaminergic neurons in D.A.T.

The effects of a long term dihydroergotoxine treatment on agonist and antagonist striatal dopamine binding sites are dose and age related.

Chronic administration of dihydroergotoxine, at the two doses of 2.5 mg/kg and 5 mg/kg decreases the binding of dopamine 3H-agonists to striatal membranes. By contrast the binding of dopamine 3H-antagonists is decreased in the animals treated with the higher dose and increased in those treated with the lower one. In old rats, in which a partial loss of both 3H-antagonist and 3H-agonist binding sites is observed, the DHT treatment confirms to increase the binding of 3H-antagonists, without affecting that of 3H-agonists. Thus, aging and ergot alkaloids seem to discrimate between DA-agonist and DA-antagonist receptor sites suggesting that this receptors are separate entityes.

[Effect of street noise on blood catecholamines, cyclic AMP and various cardiovascular and metabolic functions in a group of subjects with untreated essential hypertension]. / Effetti del rumore stradale sulle catecolamine ematiche, sul cAMP e su alcune funzioni cardio-vascolari e metaboliche in un gruppo di soggetti ipertesi essenziali non trattati.

The effect of road noise on blood catecholamines, cAMP and certain cardiovascular and metabolic parameters was studied in a group of young untreated essential hypertensives. It was found that the 10' stimulus increased both systolic and diastolic pressure values. Blood catecholamines rose only after 5'. The most significant increase was in adrenaline as opposed to noradrenaline and dopamine. Significant changes were noted in cAMP and triacylglycerols (10' and 15' after commencement of the stimulus respectively). Comparison with previous results in normotensives suggested that the catecholamine response to stress is primarily alpha-receptorial when blood pressure is normal and beta-adrenergic in hypertension.

[Effects of street noise on plasma catecholamines, cyclic AMP and various cardiovascular and metabolic functions in a group of normal subjects]. / Effetti del rumore stradale sulle catecolamine ematiche, sul cAMP e su alcune funzioni cardio-vascolari e metaboliche in un gruppo di soggetti normali.

Exposure to traffic noise for ten minutes increased diastolic pressure without affecting systolic pressure and heart rate. Plasma catecholamine levels were enhanced only five minutes after noise stimulation. Noradrenaline increased more significantly than dopamine and adrenaline. No changes in plasma cAMP levels and hematochemical parameters ( cholesterol , glucose, triglycerides , uric acids) were observed. Data suggest that traffic noise can be considered a stress-full stimulus and its effect on diastolic pressure can be correlated to alpha-receptor stimulation.

[Plasma levels of cyclic AMP and catecholamines in ischemic cerebrovascular disorders]. / Livelli plasmatici di AMP ciclico e di catecolamine nelle cerebropatie vascolari ischemiche.

We evaluated in this study the relationships between the clinical course of patients affected with ischemic cerebrovascular diseases and plasma catecholamine and cAMP levels. We compared two groups of acute and chronic patients. These results show a different behaviour of plasma catecholamine and cAMP levels. This hematochemical parameter might assume a distance prognostic significance.

Effects of bromocriptine and dopamine on the binding of estradiol to its uterine cytoplasmic receptors.

The in vivo and in vitro effects of bromocriptine on the binding of estradiol 17 beta to its specific uterine receptors were studied in both mature and immature rats. A single i.p. injection of bromocriptine reduced the specific estradiol-receptor interaction in adult rats, while it resulted ineffective in prepubertal animals. The effect of bromocriptine in mature rats was dose-dependent and evident only when using a dose of at least 0.70 mg/kg. Experiments in vitro also showed that in mature rats bromocriptine affected the estradiol-receptor interaction inducing a decrease in binding, which is well correlated to the concentration used. On the contrary, no effect of bromocriptine in vitro was observed when using cytosol obtained from uteri of immature rats. Very similar results were obtained in experiments in vitro when using dopamine instead of bromocriptine. Our results suggest that apparently there are two forms of estrogen receptors, one present both in prepubertal and pubertal age and the other present only in mature animals. The latter is the type of receptor sensitive to both bromocriptine and dopamine and presumably develops under the control of hormonal factors, which are only present at puberty.