Showing papers on "Catecholamine published in 1987"

Facilitation of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation after activation of catecholaminergic pathways or central norepinephrine injection.

Abstract: The functional role of central catecholamines in regulation of ACTH secretion remains controversial. In the present report, the nature of catecholaminergic influences was directly assessed by measurement of hypophysial-portal plasma immunoreactive CRF (irCRF) levels after activation of endogenous aminergic pathways by electrical stimulation or administration of norepineprhine (NE). Electrical stimulation of the ventral noradrenergic ascending bundle, a fiber system primarily carrying catecholaminergic fibers arising from brainstem regions, resulted in a 2.9-fold elevation of portal irCRF levels. Pretreatment with the αl-adrenergic receptor antagonist coryanthine, but not the β-adrenergic antagonist propranolol, blocked the facilitatory effect of electrical stimulation and reduced prestimulation irCRF levels by 34.7 ± 4.2% (P < 0.05). Intracerebroventricular administration of 0.1-5.0 nmol NE resulted in a dose-dependent facilitation of portal plasma irCRF levels which could be blocked by pretreatment with ...

Corticotropin-releasing factor administration elicits a stress-like activation of cerebral catecholaminergic systems

Abstract: The cerebral content of the biogenic amines, dopamine (DA), norepinephrine (NE), and serotonin (5-HT) and their catabolites 30 min after CRF or saline injections was determined using HPLC with electrochemical detection. Injection of CRF (1.0 μg) into the lateral ventricles (ICV) of mice produced a behavioral activation in which their motor movements appeared as bursts of activity followed by periods of immobility. CRF administration (ICV or SC) did not alter the concentrations of DA, NE, tryptophan, 5-HT, or 5-hydroxyindoleacetic acid (5-HIAA) in any brain region measured. ICV CRF increased the concentrations of dihydroxyphenylacetic acid (DOPAC), the major catabolite of DA, and of 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG), the major catabolite of NE, in several brain regions. DOPAC:DA ratios were consistently increased in prefrontal cortex, septum, hypothalamus, and brain stem relative to animals injected with saline. MHPG:NE ratios were also increased in the prefrontal cortex and hypothalamus, with a marginal effect (p=0.06) in brain stem. SC CRF significantly increased DOPAC:DA in prefrontal cortex, and MHPG:NE in prefrontal cortex, hypothalamus and brain stem. Pretreatment with naloxone did not prevent any of the neurochemical responses to ICV CRF, but naloxone alone increased DOPAC:DA in medial profrontal cortex, and decreased MHPG:NE in nucleus accumbens in CRF-injected mice. These results suggest that administration of CRF either centrally or peripherally induces an activation of both dopaminergic and noradrenergic systems in several regions of mouse brain. The pattern resembles that we observe in mice following stressful treatments such as footshock or restraint, but the effect of CRF on noradrenergic systems is less pronounced. Also, brain free tryptophan which is consistently increased in all brain regions by footshock or restraint was not altered by CRF. Thus CRF triggers a response in CNS catecholamine systems that resembles, but does not precisely mimic, that observed following commonly used stressors. This activation of CNS catecholamine metabolism may be related to some of the behavioral effects of CRF, but not all of them because naloxone, which prevents the effects of CRF on exploratory behavior, did not alter the catecholamine responses to CRF.

Stimulation of [3H]dopamine release by nicotine in rat nucleus accumbens.

Abstract: The mesolimbic system of the brain has been shown to be involved in the reward properties of a number of agents. It is possible that release of monoamines by nicotine in this brain area could be related to the pleasurable aspects related to cigarette smoking. In this investigation, the effect of nicotine on the release of [3H]dopamine in the nucleus accumbens of the rat was studied. It was shown that nicotine produced a concentration-dependent increase in [3H]dopamine release at concentrations of 0.1 microM and above. The increase in release was found to be almost completely calcium dependent. The nicotine-induced release was only partially blocked by the nicotinic antagonists hexamethonium and d-tubocurarine. A number of cholinergic agonists, as well as other compounds, were tested for their capacity to mimic the effect of nicotine. At equimolar concentrations there was, at most, only 50% of the activity of nicotine. The results of this study demonstrate that nicotine stimulates the release of dopamine in the nucleus accumbens at concentrations similar to those in the blood of cigarette smokers. This suggests that the release of monoamines in specific nuclei of the mesolimbic system may be an important determinant of the desire to smoke cigarettes.

Differences in tyrosine hydroxylase-like immunoreactivity characterize the mesostriatal innervation of striosomes and extrastriosomal matrix at maturity.

Abstract: Tyrosine hydroxylase [TyrOHase, tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (2-hydroxylating), EC 1.14.16.2] is the rate-limiting enzyme in the synthetic pathway of catecholamines and is expressed by neurons containing dopamine, norepinephrine, and epinephrine. TyrOHase is present in high concentrations in the caudate nucleus and putamen, where nearly all of it is contained in axons of the dopaminergic mesostriatal pathways. We have employed three different polyclonal antibodies directed against TyrOHase, one tested here for specificity by two-dimensional gel electrophoresis, to reexamine the anatomic distribution of fibers expressing TyrOHase-like immunoreactivity in the striatum of mature human, monkey, and cat brains. The findings suggest that this distribution is distinctly inhomogeneous. The macroscopic compartments known as striosomes have low TyrOHase-like immunoreactivity relative to the surrounding extrastriosomal matrix. These observations add to evidence that dopaminergic modulation of neural processing in the mature striatum is organized in accordance with striosomal architecture and suggest that part of the mechanism for such differentiation may involve presynaptic differences in enzymatic regulation of dopamine content in and out of striosomes.

The role of adrenal nerves in the regulation of adrenocortical functions.

Abstract: There is now convincing evidence for the distribution of several nerve plexuses in the outer zone of the adrenal cortex. At the ultrastructural level, the close proximity of nerve boutons to cortical cells establishes the anatomical substrate for a direct neural effect on adrenal cortical cell functions. Of those neurotransmitters and neuropeptides identified to date, catecholamine, VIP, and NPY appear to be most prevalent. Importantly, the amounts of morphologically identifiable catecholamine, VIP and NPY are differentially sensitive to alteration of several physiological conditions. Furthermore, the VIP plexus appears to be intrinsic to the adrenal while the catecholamine and NPY nerve fibers enter the adrenal along blood vessels. Together, these results suggest that these multiple nerve plexuses might exert control on several adrenocortical cellular processes in addition to the regulation of adrenal blood flow. Compensatory adrenal growth, a rapid proliferative response to unilateral adrenalectomy, was previously shown to be neurally mediated. The role of the catecholamine innervation in the mediation of this process has now been demonstrated. The elimination of the sympathetic nervous system by neonatal sympathectomy inhibited the proliferative response as measured by DNA synthesis. In vivo administration of beta-adrenergic receptor blockers did not inhibit the compensatory growth response. Furthermore, the beta-adrenergic agonist isoproterenol, inhibited the rate of DNA synthesis both in vivo and in vitro. The direct action of the beta-adrenergic agonist on the adrenocortical cell DNA synthesis rate suggests that the catecholaminergic nerves tonically inhibit cell proliferation associated with compensatory growth and that the release from the beta-adrenergic inhibition is necessary for compensatory growth. Whether inhibition of the beta-adrenergic innervation is the trigger for compensatory growth or whether it is permissive to the action of a still unidentified mitogenic substance, is not yet known. The direct role of VIP and catecholamines in the regulation of steroidogenesis has been investigated in vitro using the perifused capsule-glomerulosa preparation which is representative of a normal outer zone of the adrenal and is the site of the neural plexuses and identified receptors. Both VIP and isoproterenol stimulate steroidogenesis and specifically cause a greater increase in secretion of aldosterone than corticosterone. Although the concentrations of VIP and isoproterenol required to stimulate steroidogenesis are greater than reported circulating levels, release from resident nerves could provide high local concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasma norepinephrine levels in infants and children with congestive heart failure

Abstract: To characterize the sympathetic nervous system response to congestive heart failure (CHF) in infants and children, plasma catecholamine levels were measured in 102 subjects undergoing routine cardiac catheterization (mean age 3.3 years, range 0.1 to 14.7), including 61 with left-to-right shunts. Plasma norepinephrine levels were significantly higher (p less than 0.0001) in children with CHF than in those without CHF. A highly significant association (p less than 0.0001) was found between the level of plasma norepinephrine and severity of CHF symptoms. This relation was found for CHF secondary to lesions producing a left-to-right shunt and CHF resulting from primary myocardial dysfunction. In congenital lesions with a left-to-right shunt, plasma norepinephrine levels correlated well with size of the shunt (Qp/Qs) (r = 0.75, p less than 0.001) and degree of pulmonary arterial hypertension (r = 0.70, p less than 0.001). Elevation of plasma norepinephrine concentrations in infants and children are seen with severe CHF regardless of its origin.

Cardiovascular, ventilatory and catecholamine responses to maximal dynamic exercise in partially curarized man.

Abstract: 1. In ten young men the ventilatory, cardiovascular, catecholamine and metabolic responses to maximal dynamic leg exercise on a stationary bicycle were followed during partial neuromuscular blockade with tubocurarine. Maximal exercise was performed when the drug effect was at its maximum as well as during the subsequent reduction in the effect allowing a gradually increasing work intensity. The results were compared with those obtained during submaximal and maximal exercise performed without tubocurarine. Partial neuromuscular blockade decreased hand-grip strength to 41 +/- 1.1% (S.E. of mean) and the maximal work load to 27 +/- 2.4% of control values. Voluntary effort was maximal and the rate of perceived exertion was high at all levels of exercise with tubocurarine indicating a maintained intense central nervous motor command. 2. During maximal action of the drug oxygen uptake was 1.67 +/- 0.11 l/min while only 0.91 +/- 0.13 l/min (P less than 0.01) at the same work intensity without neuromuscular blockade. This difference may reflect a dominant reliance on fast-twitch muscle fibres when work was performed under the influence of tubocurarine. 3. Compared at a given oxygen uptake ventilation was higher during work with tubocurarine than during control exercise (e.g. 55 +/- 4.2 and 40 +/- 2.2 l/min, respectively (P less than 0.01), at a mean oxygen uptake of 1.9 l/min), while heart rate did not differ significantly (146 +/- 4.4 and 139 +/- 3.0 beats/min). With decreasing drug effect both variables increased towards the maximum values of 138 +/- 4.5 l/min and 183 +/- 3.9 beats/min, respectively, achieved in control experiments at an oxygen uptake of 3.8 +/- 0.2 l/min. Like heart rate the mean arterial blood pressure increased with increasing work load and was similar at a given oxygen uptake with and without tubocurarine. 4. During maximal exercise at peak tubocurarine effect plasma adrenaline and noradrenaline concentrations were smaller than during control maximum, 1.6 +/- 0.27 versus 3.4 +/- 0.55 nmol/l (P less than 0.01) and 7.5 +/- 1.3 versus 12.6 +/- 1.8 nmol/l (P less than 0.05), respectively. However, comparisons at identical oxygen uptake rates revealed that catecholamine responses were markedly enhanced during tubocurarine treatment. Also, blood lactate concentrations were smaller at peak tubocurarine action than during control maximum, 1.9 +/- 0.42 mmol/l and 6.1 +/- 0.49 mmol/l (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Separate areas of rat medulla oblongata with populations of serotonin- and adrenaline-containing neurons alter blood pressure after L-glutamate stimulation.

Abstract: Separate populations of serotonin- and adrenaline-containing neurons exist in the ventrolateral medulla oblongata and project to the intermediolateral cell column of the spinal cord. The medullary serotonin nuclei appear to constitute a heterogeneous group with diverse effects on arterial pressure. Microinjections of sodium glutamate (which excites cell bodies but not axons of passage) made in the area of the ventrolateral serotonin cells evokes an increase in arterial pressure which is abolished by prior 5,7-dihydroxytryptamine (5,7-DHT) treatment. In contrast, glutamate microinjection in the area of the serotonin-containing cell bodies in the midline of the medulla evokes falls in arterial pressure and these responses are attenuated by pretreatment with 5,7-DHT. Glutamate microinjection made in the ventrolateral medulla in the area of the adrenaline-containing cells, evokes increases in arterial pressure which are not altered by 5,7-DHT pretreatment. After ablation of the area of the adrenaline-containing cells by electrolytic lesion, the pressor function of the ventrolateral serotonin-containing cells is still observed. These results suggest that although the serotonin-containing neurons of the ventrolateral medulla are closely aligned with the ventrolateral adrenaline area, the serotonin cell groups and the cells of the adrenaline area exert their pressor actions independently.

The corticotropin-releasing factor release in rat hypophysial portal blood is mediated by brain catecholamines.

Abstract: In order to study the involvement of the hypothalamic corticotropin-releasing factor (CRF) in catecholamine-induced adrenocorticotropin (ACTH) secretion, we have measured CRF levels in rat hypophysial portal blood (HPB) after the pharmacological destruction of the ventral noradrenergic bundle (VNAB), using 6-hydroxydopamine (6-OHDA) stereotaxically injected into the VNAB. CRF levels in HPB were measured by radioimmunoassay, and the effects of 6-OHDA injection were controlled by the determination of catecholamine concentrations in the total hypothalamus. VNAB lesions induced a dramatic decrease in norepinephrine and epinephrine hypothalamic concentration. The CRF levels in HPB were also significantly reduced. These results suggest that central catecholamines exert a direct stimulatory control on the CRF release and play a major role in stress-induced ACTH secretion.

Effects of intraventricular injections of galanin on neuroendocrine functions in the male rat. Possible involvement of hypothalamic catecholamine neuronal systems.

Abstract: Galanin-catecholamine interactions have been analysed within the hypothalamus and the anteromedial frontal cortex of male rats by means of quantitative histofluorimetrical and biochemical measurements of catecholamine fluorescence in discrete catecholamine nerve terminal systems and measurements of serum levels of adenohypophyseal hormones and corticosterone using radio-immunoassay determinations. 125I-galanin binding sites were analysed and related to the distribution of galanin-immunoreactive neuronal structures in the median eminence and paraventricular hypothalamic nucleus. The results show that intraventricular injections of galanin in the awake and unrestrained male rat produce rapid increases of prolactin and growth hormone secretion but no effects on serum luteinizing hormone, thyroid stimulating hormone or on corticosterone levels. These changes in neuroendocrine function were associated with a selective reduction of the catecholamine stores in the medial palisade zone of the median eminence at the 20 min time interval. 125I-galanin binding sites were found throughout the hypothalamus including the median eminence and the magnocellular part of the paraventricular hypothalamic nucleus with a good correspondence with galanin immuno-reactivity. It is suggested that the enhancement of prolactin secretion induced by galanin involves an interaction between galanin and dopamine in the medial palisade zone leading to a reduced synthesis and/or release of dopamine and thus to a reduced prolactin inhibitory activity and to increases in prolactin secretion. A possible involvement of hypothalamic catecholamines in the galanin-induced changes of growth hormone secretion remains to be established.

In-vivo evaluation of dopamine receptor-mediated inhibition of gonadotrophin secretion from the pituitary gland of the goldfish, Carassius auratus.

Abstract: Dopamine acts directly on the pituitary to modulate gonadotrophin (GtH) secretion in goldfish (Carassius auratus). In the light of this important role for dopamine in the regulation of goldfish reproduction, this investigation was designed to evaluate the receptor specificity of this dopamine inhibition and to describe the use of domperidone, a specific dopamine D2-receptor antagonist, in the manipulation of pituitary function in goldfish. To investigate the specificity of dopamine inhibition of GtH secretion, selected dopamine receptor antagonists were injected i.p. to block dopamine receptors thereby increasing GtH secretion as reflected by increased serum concentrations of GtH. Serum GtH levels were significantly increased by the active stereoisomer (-)-sulpiride in a dose-related fashion; (+)-sulpiride had no effect. Comparison of dopamine antagonists at low doses indicated that only domperidone and pimozide caused significant increases in serum concentrations of GtH. Dopamine antagonists potentiated the action of a gonadotrophin-releasing hormone analogue (GnRH-A) with an order of potency of domperidone = pimozide greater than metoclopramide = fluphenazine. [3H]Domperidone, injected i.p. with unlabelled domperidone, entered the blood and achieved maximum concentrations 12 h after injection, but did not accumulate in the brain in appreciable amounts. Gonadal 3H radioactivity was usually equal to or in excess of blood radioactivity, while [3H]domperidone was highly concentrated in the pituitary in a time-dependent fashion, with maximal accumulation occurring 24 h after injection. The time-course of pituitary accumulation of [3H]domperidone correlated well with the temporal increase in serum GtH levels in response to i.p. injected domperidone or domperidone plus an analogue of LHRH. Domperidone increased serum concentrations of GtH in a dose-related fashion; an analogue of salmon GnRH (sGnRH-A) increased the sensitivity and magnitude of the serum GtH response to domperidone. Serum concentrations of GtH were increased by sGnRH-A in a dose-related fashion; a low dose of domperidone substantially increased the sensitivity of the serum GtH response to sGnRH-A. These results indicate that dopamine inhibits GtH secretion from the goldfish pituitary by acting through a specific mechanism mediated by a dopamine D2 receptor. Domperidone increased serum concentrations of GtH, potentiated the action of gonadotrophin-releasing hormones and did not pass into the brain after i.p. injection into goldfish. The data also suggest that dopamine and GnRH, although acting through different receptors, influence the effect of each other on GtH release.

Physical stress and catecholamine release

Abstract: In both health and disease, noradrenaline and adrenaline concentrations in plasma increase with intensity and duration of exercise (Figure 1). These changes are only to a minor extent due to decreased catecholamine clearance (Figure 2). The increase in sympathoadrenal activity during exercise is primarily elicited by feed-forward stimulation from motor centres in the brain (Figure 3, Table 1), and by afferent impulses from working muscles (Figure 4). During continued exercise, changes in internal milieu may enhance the catecholamine response. Of particular interest from a metabolic point of view is the fact that during exercise a decrease in plasma glucose causes a relatively large increase in plasma adrenaline (Figure 5). Sympathoadrenal activity is of major importance for exercise capacity. By depressing insulin secretion, as well as by direct effects on target tissues, sympathoadrenal activity enhances mobilization of glycogen as well as triglyceride from both extra- and intramuscular depots. After training, noradrenaline responses to given absolute work loads are reduced, while responses to given relative loads, i.e. work load in percent of individual work capacity, VO2/VO2max%, are unchanged. Prolonged endurance training may increase the size and secretory capacity of the adrenal medulla (Figure 7, Table 2), an adaptation which may improve exercise capacity. Differences in catecholamine levels cannot explain the fact that physically-active individuals have a lower cardiac mortality than inactive ones.

CRF initiates biological actions within the brain that are observed in response to stress

Abstract: Corticotropin-releasing factor (CRF) is thought to be an endogenous mediator of adrenocorticotropic hormone release following stress. We examined if CRF initiates further biological actions that are observed in response to stressful events. Male beagle dogs (10-12 kg) were fitted with a chronic intracerebroventricular cannula, intra-arterial and intravenous catheters, as well as a gastric fistula. Synthetic human CRF was microinjected into the third cerebral ventricle in conscious animals. CRF (0.1-1.0 nmol/kg) significantly (P less than 0.01) increased plasma concentrations of epinephrine, norepinephrine, glucagon, and glucose and elevated mean arterial pressure and heart rate. Pretreatment of the animals with the ganglionic blocking agent chlorisondamine completely abolished the increases in plasma catecholamine and glucose concentrations as well as the elevations in blood pressure and heart rate. CRF significantly (P less than 0.01) inhibited gastric acid secretion, but not plasma gastrin concentrations stimulated by an 8% liquid peptone meal. The gastric inhibitory action of CRF was completely prevented by chlorisondamine and, in part, by naloxone and a vasopressin antagonist. In contrast, bilateral truncal vagotomy did not affect the gastric inhibitory action of CRF. The results of this study indicate that CRF acts within the central nervous system to increase plasma glucose and glucagon concentrations, mean arterial pressure, and heart rate by activation of the autonomic nervous system. CRF inhibits meal-stimulated gastric acid secretion by activation of the sympathetic nervous system and, in part, by opiate and vasopressin-dependent pathways and not by inhibition of gastrin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic dissection of dopamine and serotonin synthesis in the nervous system of Drosophila melanogaster

Abstract: Catecholamine- and serotonin-containing neurons were studied in pale, a Drosophila third-chromosome recessive lethal mutant. Using histofluorescent and immunocytochemical techniques, we show that this mutation only alters catecholamine levels in the CNS. Both the presence of catecholamine-neurons and the expression of serotonin are not affected by the mutation. Furthermore, we show that normal characteristics of catecholamine neurons, such as the presence of the enzyme DOPA decarboxylase and the selective uptake properties are normal in pale mutants. We suggest that pale is either the tyrosine hydroxylase structural gene, or a gene controlling tyrosine hydroxylase activity in Drosophila. The similar genetic location of the putative tyrosine hydroxylase gene and the mutation pale supports the former suggestion.

Insulin-induced hypoglycemia activates the release of adrenocorticotropin predominantly via central and propranolol insensitive mechanisms.

Abstract: The dynamic patterns of pituitary-adrenocortical and sympatho-adrenal hormone responses to insulin hypoglycemia as well as the relative importance of central vs. peripheral control of hypoglycemia-induced ACTH secretion were evaluated. In conscious rats bearing indwelling cannulae, the changes in hormone concentrations after insulin injection were dependent on the changes in blood glucose levels with respect to both time course and magnitude. ACTH, corticosterone, epinephrine, and norepinephrine levels were found to be maximal at 60 min after 2.5 IU kg-1 insulin injected ip, whereas earlier (20 min) but smaller increases were obtained in response to 0.5 IU kg-1 insulin injected iv. In rats 6-7 days after lesions of the medial basal hypothalamus (MBH), the rise of ACTH during insulin hypoglycemia was markedly inhibited and corticosterone levels were significantly reduced. Simultaneously, the hypoglycemia-induced increase in plasma epinephrine was unchanged and that in plasma norepinephrine was significantly enhanced in rats with the MBH destroyed. The beta-adrenoreceptor blocker propranolol did not inhibit ACTH and corticosterone responses to hypoglycemia in either sham-operated or MBH-lesioned animals. We conclude that the main factors triggering ACTH release during insulin-induced hypoglycemia are of central rather than peripheral origin. The high concentrations of circulating catecholamines occurring during insulin hypoglycemia are not responsible for pituitary-adrenocortical activation by direct, beta-adrenoreceptor mediated action at the pituitary level.

Effect of fetal adrenalectomy on catecholamine release and physiologic adaptation at birth in sheep.

Abstract: Plasma catecholamine levels increase dramatically at birth. To determine the contribution of adrenal catecholamine secretion to the surge in catecholamines at birth and the role in newborn adaptation, we performed surgical adrenalectomy or sham operation on near-term ovine fetuses. After recovery in utero, the animals were delivered and supported by mechanical ventilation. Plasma catecholamine levels, heart rate, blood pressure, cardiac output, pulmonary function, surfactant secretion, and release of free fatty acids (FFA) and glucose were compared in control and adrenalectomized animals. Plasma epinephrine increased rapidly at birth in controls but was undetectable in adrenalectomized animals. Norepinephrine levels were not statistically different. Heart rate, blood pressure, cardiac output and contractility increased abruptly after cord cutting in controls but did not increase in adrenalectomized animals. Lung compliance, pulmonary function, surfactant pool size, glucose and FFA levels were significantly decreased in adrenalectomized animals. These results suggest that adrenal epinephrine secretion is vital to many of the adaptive events at birth.

Effect of dopamine-depleting brain lesions in rat pups: role of striatal serotonergic neurons in behavior.

Abstract: Previous results from our laboratory have demonstrated that 3-day-old rats given dopamine (DA)-depleting brain lesions are spared the severe behavioral dysfunctions seen after comparable brain damage in adults. This behavioral sparing is accompanied by a sprouting of serotonin (5-HT)-containing neurons in the striatum. The present results extend these observations by demonstrating that rats given the brain lesions as 15- or 27-day-olds continue to suckle, wean, and grow into adulthood without exhibiting any obvious behavioral dysfunctions, yet striatal 5-HT levels do not increase. Moreover, combined destruction of DA- and 5-HT-containing neurons in 3-day-old rat pups also produced no obvious behavioral dysfunctions. These and other results indicate that increases in striatal 5-HT are not necessary for the behavioral sparing observed after DA-depleting brain lesions in neonatal rats.

Effects of Newcastle disease virus administration to mice on the metabolism of cerebral biogenic amines, plasma corticosterone, and lymphocyte proliferation

Abstract: Newcastle disease virus (NDV) administration to mice increased concentrations of plasma corticosterone, with a maximal effect at 8 h. This elevation of plasma corticosterone concentrations was not observed in hypophysectomized animals in which the completeness of the hypophysectomy was verified by functional tests. NDV administration consistently increased concentrations of free tryptophan in all brain regions examined (prefrontal cortex, hypothalamus, and brain stem). It also caused an activation of cerebral catecholamine and indoleamine metabolism as determined by measurement of the amines and their catabolites. 3-Methoxy,4-hydroxyphenylethyleneglycol (MHPG), the major catabolite of norepinephrine (NE), homovanillic acid (HVA), a major catabolite of dopamine (DA), and 5-hydroxyindoleacetic acid (5-HIAA), the major catabolite of serotonin (5-HT), were all increased in both hypothalamus and brain stem. Ratios of catabolites to the parent amine, considered to be an index of utilization of the neurotransmitters, were increased for NE, DA, and 5-HT in the hypothalamus and for DA and 5-HT in the brain stem. This pattern of changes resembles that observed following stressors such as footshock or restraint. There were also significant increases of tryptophan, HVA, dihydroxyphenylacetic acid (DOPAC), and 5-HIAA in hypophysectomized relative to sham-operated mice. The NDV treatment also increased thymus weights and markedly decreased the proliferative responses of isolated spleen cells to phytohemagglutinin, concanavalin A, pokeweed mitogen, and Escherichia coli lipopolysaccharide. These changes were not caused by increased circulating corticosterone because they were present at equal magnitude in hypophysectomized mice. Thymosin α1 concentrations in the plasma were not altered by NDV or hypophysectomy. These results indicate that administration of NDV to mice can initiate neurochemical and endocrine responses like those observed during stress and can also cause immunosuppression. They are thus consistent with the hypothesis that a virus can be a stressor.