P. Preziosi

Effect of midbrain raphe lesion or 5,7-dihydroxytryptamine treatment on the prolactin-releasing action of quipazine andd-fenfluramine in rats

The role of brain serotonin in regulating prolactin (PRL) secretion has been investigated by studying the effect of quipazine and D-fenfluramine, two serotonin-like drugs, on plasma PRL levels under various experimental conditions. Quipazine (5, 10 and 20 mg/kg i.p.) and D-fenfluramine (5, 7.5 and 10 mg/kg i.p.) induced dose-related increases in plasma PRL levels in male rats. Intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) or electrolytic lesion of the nucleus raphe medianus (MR), which caused a marked and selective depletion of hypothalamic serotonin levels, significantly reduced the PRL-releasing effect of both quipazine and D-fenfluramine. These results suggest that the effect of these drugs on PRL release is mediated through a serotonergic mechanism in the brain.

Influence of restraint stress, corticosterone and betamethasone on brain amine levels(*)

Summary The changes in brain 5-HT, dopamine and noradrenaline levels provoked by restraint stress, do not seem to be due to the negative feedback effect of endogenous corticosterone.

Effect of selective degeneration of brain serotonin-containing neurons on plasma corticosterone levels: Studies with d-fenfluramine

Summary The effect of selective lesion of brain serotonergic neurons on the corticosterone releasing action of d-fenfluramine were studied in male rats. Raphe lesion, which selectively decreased brain 5-HT, prevented the effect of the d-fenfluramine on corticosterone secretion. An intraventricular injection of 5,7-dihydroxytryptamine, in desipramine-pretreated rats, which caused a substantial damage to central serotonergic systems without affecting catecholamine-containing neurons, also blocked the stimulatory effect of d-fenfluramine on corticosterone release. These findings are compatible with the hypothesis that brain 5-HT plays a stimulatory role in the control of hypothalamic-hypophyseal-adrenal axis in the rats.

Chromaffin cells: the peripheral brain

Chromaffin cells probably are the most intensively studied of the neural crest derivates. They are closely related to the nervous system, share with neurons some fundamental mechanisms and thus were the ideal model to study the basic mechanisms of neurobiology for many years. The lessons we have learned from chromaffin cell biology as a peripheral model for the brain and brain diseases pertain more than ever to the cutting edge research in neurobiology. Here, we highlight how studying this cell model can help unravel the basic mechanisms of cell renewal and regeneration both in the central nervous system (CNS) and neuroendocrine tissue and also can help in designing new strategies for regenerative therapies of the CNS.

Effect of quipazine and d-fenfluramine, two serotonin-like drugs, on TSH secretion in basal and cold stimulated conditions in the rat

Abstract The effects of two serotonin-like drugs, quipazine and d-fenfluramine, on thyroid stimulating hormone (TSH) secretion in basal and cold stimulated conditions were investigated in male rats. Both drugs are able to decrease TSH secretion in basal conditions and to inhibit the TSH rise elicited by cold exposure (CE). These effects were antagonized by a pretreatment with metergoline, a serotonin receptor blocker. These results appear to suggest that serotonin may play an inhibitory role in the control of TSH secretion in the rat.

Effect of selective lesioning of serotonin-containing neurons on the TSH-inhibiting action of d-fenfluramine in male rats.

Abstract The effects of selective lesion of brain serotoninergic neurons on the TSH inhibiting action of d-fenfluramine were studied in male rats. Raphe lesion, which selectively decreased brain 5-HT, prevented the effect of d-fenfluramine on TSH secretion. An intraventricular injection of 5, 7-dihydroxytryptamine (150 μg in 20 μ1), in desipramine-pretreated rats, which caused a substantial damage to central serotoninergic systems without affecting catecholamine- containing neurons, also blocked the inhibitory effect of d-fenfluramine on TSH release. These findings are compatible with the hypothesis that brain 5-HT plays an inhibitory role in the control of TRH-TSH secretion in male rats.

Role of Brain Noradrenaline in the Tonic Regulation of Hypothalamic Hypophyscal Adrenal Axis

Publisher Summary This chapter discusses the role of central nervous system in the regulation of synthesis and release of corticotrophin (ACTH). The chapter gives evidence in favor of a central noradrenergic system that inhibits ACTH secretion via a-receptorial stimulation. In dogs, the injection into the third ventricle of catecholamine precursors, catecholamines and drugs that release or protect catecholamines from inactivation, inhibits stress-induced adrenocortical activation. In rats, drugs that decrease brain catecholamine levels provoke adrenocortical activation, also when injected directly into the third ventricle of systemically ineffective doses. Specific depletion of noradrenaline but not of dopamine is able to cause increase of plasma corticosterone. Experiments concerning long-term catecholamine depletion, suggest the presence of a small, defined, functional pool of noradrenaline responsible for the tonic inhibition of ACTH secretion. Although a corticotrophin-releasing factor (CRF) is not chemically identified and synthesized, the neurovascular hypothesis of ACTH secretory cell regulation seems to be well founded. A possible role of brain catecholamines in the regulation of ACTH secretion is considered by numerous investigators.

Lack of evidence for an inhibitory role played by tuberoinfundibular dopaminergic neurons on TSH secretion in the rat.

The role of dopamine (DA) in the control of thyroid stimulating hormone (TSH) secretion in basal or cold stimulated conditions was investigated by using pharmacological or neurosurgical tools. The intraventricular injection of DA (5 micrograms/animal) or the subcutaneus (s.c.) injection of a dopaminomimetic agent failed to induce changes of TSH plasma levels in normal or in cold stimulated conditions. The same results were obtained by intraperitoneal (i.p.) administration of haloperidol, a blocker of dopaminergic receptors. The complete deafferentation of hypothalamus, which causes degeneration of norepinephrinergic nerve endings and leaves the DA tuberoinfundibular system unaffected, prevented the TSH release evoked by cold exposure. alpha-Methyl-p-tyrosine (alpha-MpT) (250 mg/kg i.p.), which causes a remarkable reduction of DA in the median eminence (ME) of deafferented animals, was unable to restore the TSH response to cold. Collectively these results seem to suggest that DA does not play a significative role in the control of TSH secretion in the rat.

Brain serotonin depletors and adrenocortical activation

Abstract p -Chlorophenylalanine, prenylamine and α-methyldopa are brain serotonin depletors. The first acts in an elective manner; if administered to the rat by the routes and at doses which cause a marked reduction in the content of cerebral 5-hydroxy-tryptamine, it does not bring about adrenocortical activation either at the time when there is maximum depletion of brain serotonin or later. The adrenocortical activation provoked by prenylamine given i.v. may be related to the acute hypotension which the drug produces. Data obtained did not corroborate the importance of brain serotonin depletors in the liberation of CRF and consequent activation of the pituitary-adrenal axis.

Brain and liver tryptophan pathways and adrenocortical activation during restraint stress

Summary In rats under restraint stress the following occurs as opposed to controls: a) increase in plasma corticosterone concentration; b) increase in liver tryptophan-pyrrolase activity; c) decrease in brain 5-HT, not correlated with the duration of the restraint; d) decrease in brain 5-HIAA during the first hour followed by a progressive increase. These results demonstrate that during the adreno-cortical activation caused by stress the tryptophan shunt from the serotonin to the kynurenine pathway is almost abolished. This probably occurs because during stress there are a greater number of precursors available which may satisfy both the brain and liver metabolic pathways.