Brain Serotoninergic System Research Articles

Effect of domoic acid on metabolism of 5-hydroxytryptamine in rat brain.

Domoic acid (Dom) is a neurotoxic secondary amino acid that interacts with the glutamate receptors, producing neurological problems. In the present work, we study the effects of Dom on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete rat brain regions. The effects of Dom on the brain metabolism of serotonin are also discussed in this paper. Dom stimulates the rat brain serotoninergic system, increasing differentially the synthesis and the catabolism of 5-HT and the elimination of 5-HIAA.

Propranolol-induced increases in target-biting attack

The effect of a beta-adrenoreceptor blocking agent on defensive aggression in mice was evaluated. Acute doses of d, l-propranolol (0.2, 0.4, 0.8, 1.6, 3.2, 6.4, and 12.8 mg/kg) were administered to male Rockland-Swiss mice prior to testing in a target-biting paradigm. Baseline conditions established a high target-biting rate immediately after animals received a 2 mA tail shock, an intermediate biting rate during a 2-min intershock interval, and a low biting rate during a 15-s tone stimulus preceding the next shock. Every dose of propranolol increased target-biting rates above baseline during each interval with one exception: 0.4 mg/kg decreased the biting rate immediately after delivery of the tail shock. The overall increase in aggression observed following dosing with propranolol was not expected from a review of the clinical literature. These results are discussed in reference to propranolol's known effects on the brain serotoninergic systems and the use of animal model of defensive aggression.

THE EFFECT OF ELECTRICAL STIMULATION OF THE EAR POINTS ON THE PLASMA ACTH AND GH LEVEL IN HUMANS

The effect of electrical stimulation of the ear points on the plasma ACTH and GH level was investigated in healthy female subjects. Electrical stimulation by 20 pulses/sec for 20 min. induced an elevation of plasma GH; however, no changes were found in the plasma level of ACTH at 20 min. after the needle removal. The mechanism of action of electroacupuncture in inducing GH secretion may involve the brain endorphin, serotoninergic and catecholaminergic systems. The results obtained from the determination of ACTH suggest the conclusion that electroacupuncture did not induce stress and the increased level of GH may be due to specific effects of electrical stimulation on the neuroendocrine processes.

Peripheral and central mechanisms of action of serotoninergic anorectic drugs

Several pieces of evidence indicate that brain serotoninergic systems play an inhibitory role in feeding, being specifically involved in regulating satiety and food selection. The anorectic drug fenfluramine has been shown to exert its effects by activating serotoninergic mechanisms. Since fenfluramine influences both central and peripheral serotonin stores, it is difficult to establish the relative contributions of the central and peripheral serotoninergic mechanisms in the regulation of feeding behaviour. In the present paper evidence is presented that changes in feeding come about In the present paper evidence is presented that changes in feeding come about after interventions in either the brain or the periphery. This evidence includes the observation that serotonin itself given subcutaneously causes a dose-related anorexia in rats trained to eat four hours a day, an effect antagonized not only by metergoline but also by xilamidine, a serotonin antagonist that does not cross the blood-brain barrier. Since serotonin given systemically cannot reach the brain, its effect is ascribed to the activation of peripheral mechanisms. Furthermore, as is the case with fenfluramine, subcutaneous administration of serotonin is able to completely counteract the overeating induced by the glucoprivic agents insulin and 2-deoxy-D-glucose (2-DG). It is concluded that activation of peripheral serotoninergic mechanisms is sufficient not only to reduce eating in rats trained to eat four hours a day, but also to control the hyperphagias brought about by insulin or 2-DG.

Effect of destruction of the brain serotoninergic system on alcohol intake by rats in the early stages of experimental alcoholism

Effect of destruction of the brain serotoninergic system on alcohol intake by rats in the early stages of experimental alcoholism

Hippocampal cell nuclear binding of corticosterone following 5,7-dihydroxytryptamine

Adult male rats were injected into the lateral brain ventricle with 5,7-dihydroxytryptainine (5,7-DHT). They were adrenalectomized 5–7 days later and, following an additional 24 h, the specific in vitro [ 3H]corticosterone binding capacity of dorsal hippocampal slices was determined by estimation of uptake of radioactivity by the nuclear fraction. Specific corticosterone (CS) binding was reduced by 50–70% in the neurotoxin-treated as compared to vehicle-injected animals. Brain serotonin and 5-hydroxyindoleacetic acid concentrations were depleted by 50–70% in the 5,7-DHT-injected rats. These results suggest that the maintenance of normal dorsal hippocampal CS binding capacity is dependent upon the integrity of endogenous brain serotoninergic neuronal systems.

Effect of melatonin on induction of ovulation in the light- induced constant estrous-anovulatory syndrome and possible role of the brain serotoninergic system.

Continuous light (CL) induces constant estrous anovulatory (CEA) syndrome and blockade of pineal gland activity. Chronic treatment with metatonin is able to overcome the anovulatory state in about 70% of CL-CEA rats, and the luteinizing effect of melatonin is significantly counteracted either by feeding the animals with a tryptophan-poor diet or by injecting methiothepin, a blocker of central serotoninergic receptors. It appears that melatonin elicits luteinization in CL-CEA rats through the brain serotoninergic system.

Dose-dependent dual effect of corticosterone on cerebral 5-HT metabolism

The action of 1.0 and 10.0 mg/kg (i.p.) of corticosterone on serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents and on serotonin turnover, measured by an MAO-inhibitor method, was studied at 30 and 120 min after administration. A 1.0 mg/kg dose of corticosterone increased the serotonin content and turnover in the hypothalamus and mesencephalon 30 min after administration; however, it was ineffective on dorsal hippocampus and frontal and parietal cortex. 5-HIAA content did not change significantly in any of the brain areas studied. A 10.0 mg/kg dose of corticosterone decreased the serotonin content and turnover in the hypothalamus and mesencephalon; it was ineffective in other brain areas investigated. 5-HIAA content significantly decreased in the hypothalamus while it increased in the mesencephalon and dorsal hippocampus. In the parietal and frontal cortex, 5-HIAA content did not change following administration of 10.0 mg/kg of corticosterone. At 120 min after corticosterone administration, neither 5-HT content and turnover nor 5-HIAA content showed any change in the brain areas investigated. The results suggest that corticosteroids might change the activity of the brain serotoninergic system in a dose- and time-dependent manner, and in this way the serotoninergic system might play an important role in mediation of the corticosteroid effect exerted on brain function.

L-Tryptophan and neuroendocrine regulation in neurologic patients: Hormone responses to l-tryptophan loading in patients with hypothalamic lesions

1. Oral administration of 2 g of l-tryptophan induced a marked plasma elevation of total and free tryptophan during the 2 hr of sampling in both normal subjects and in neurologic patients. Plasma free trytophan concentration showed a peak about 60 min after loading with l-tryptophan. 2. Plasma immunoreactive follitrophin (FSH) and lutrophin (LH) levels were not altered after l-tryptophan treatment. 3. Plasma immunoreactive somatotrophin (growth hormone, GH) levels showed a statistically significant elevation after l-tryptophan loading in both normal subjects and in neurologic control patients. In two acromegalic patients there was a very marked elevation of plasma somatotrophin levels 90 min after loading. No responses of plasma somatotrophin to l-tryptophan were observed in patients with hypothalamic lesion or with hypopituitarism. 4. Plasma cortisol levels showed significant morning decline during loading either with l-tryptophan or with l-leucine as placebo in normal subjects and in neurologic control patients. In patients with hypothalamic lesion the monitoring of plasma cortisol concentrations during l-tryptophan loading revealed a primary elevation with a subsequent slight decline. No variation of plasma cortisol was found in patients with hypopituitarism. 5. It was concluded that the brain serotoninergic system can be activated by l-tryptophan treatment which results in alterations of the hypothalamic regulation of somatotrophin secretion. When neuroendocrine dysfunction is due to structural lesions in the hypothalamus or in related regions, l-tryptophan loading is unable to modify somatotrophin secretion. The normal morning decline of plasma cortisol levels is lacking in such patients.

Stimulatory role for brain serotoninergic system on prolactin secretion in the male rat.

Systemic administration of parachlorophenylalanine (PCPA, 100 mg/kg sc on alternate days X two times), a blocker of serotonin (5-HT) synthesis, considerably decreased brain 5-HT and plasma prolactin (PRL) levels in young male rats. Intraventricular (IVT) administration of 5,7-dihydroxytryptamine (5,7-DHT, 200 mug/20 mul), a neurotoxic drug which destroys 5-HT nerve terminals, induced, 3, 12, and 30 days after treatment, a marked depletion of brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and considerably reduced plasma PRL levels at each time interval. Feeding of rat for up to 4 days with a tryptophan (TP)-deficient diet, caused a depletion of brain 5-HT and 5-HIAA contents and did not modify plasma PRL levels. Addition of TP (2 g/kg of diet) to the TP-deficient diet resulted in increased brain 5-HT and 5-HIAA contents and significantly increased PRL levels. These data provide evidence for the role of the 5-HT system in the maintenance of tonic PRL secretion.