Changes In Catecholamine Metabolism Research Articles

COMTVal158Met Genotype Affects Complex Emotion Recognition in Healthy Men and Women.

The catechol-o-methyltransferase (COMT) gene has repeatedly been shown to change amygdala activity and amygdala-prefrontal connectivity during face processing. Although the COMT gene appears to induce a negativity bias during the neural processing of faces, it is currently unclear whether a similar negativity bias emerges during the behavioral processing of faces. To address this issue, we investigated differences in complex emotion recognition between participants (n = 181) that had been a priori genotyped for functional polymorphisms of the COMT (Val158Met) and serotonin transporter (5-HTTLPR) gene. We were, thus, able to analyze differences in face processing on basis of participants’ COMT genotype while controlling for participants’ 5-HTTLPR genotype. Variations of participants’ COMT but not 5-HTTLPR genotype accounted for differences in participants’ emotion recognition performance: Met/Met carriers and Met/Val carriers were more accurate in the recognition of negative, but not neutral or positive, expressions than Val/Val carriers. We, therefore, revealed a similar negativity bias during the behavioral processing of faces that has already been demonstrated during the neural processing of faces, indicating that genotype-dependent changes in catecholamine metabolism may affect face processing on the behavioral and neural level.

Effects of transgenic expression of dopamine beta hydroxylase (Dbh) gene on blood pressure in spontaneously hypertensive rats.

The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and left ventricular hypertrophy. Catecholamines play an important role in the pathogenesis of both essential hypertension in humans and in the SHR. Recently, we obtained evidence that the SHR harbors a variant in the gene for dopamine beta hydroxylase (Dbh) that is associated with reduced adrenal expression of Dbh mRNA and reduced DBH enzymatic activity which correlated negatively with blood pressure. In the current study, we used a transgenic experiment to test the hypothesis that reduced Dbh expression predisposes the SHR to hypertension and that augmentation of Dbh expression would reduce blood pressure. We derived 2 new transgenic SHR-Dbh lines expressing Dbh cDNA under control of the Brown Norway (BN) wild type promoter. We found modestly increased adrenal expression of Dbh in transgenic rats versus SHR non-transgenic controls that was associated with reduced adrenal levels of dopamine and increased plasma levels of norepinephrine and epinephrine. The observed changes in catecholamine metabolism were associated with increased blood pressure and left ventricular mass in both transgenic lines. We did not observe any consistent changes in brainstem levels of catecholamines or of mRNA levels of Dbh in the transgenic strains. Contrary to our initial expections, these findings are consistent with the possibility that genetically determined decreases in adrenal expression and activity of DBH do not represent primary determinants of increased blood pressure in the SHR model.

Effects of Swim Stress and Fluoxetine on 5-HT1A Receptor Gene Expression and Monoamine Metabolism in the Rat Brain Regions

Changes in gene expression of the brain serotonin (5-HT) 1A receptors may be important for the development and ameliorating depression, however identification of specific stimuli that activate or reduce the receptor transcriptional activity is far from complete. In the present study, the forced swim test (FST) exposure, the first stress session of which is already sufficient to induce behavioral despair in rats, significantly increased 5-HT1A receptor mRNA levels in the brainstem, frontal cortex, and hippocampus at 24h. In the brainstem and frontal cortex, the elevation in the receptor gene expression after the second forced swim session was not affected following chronic administration of fluoxetine, while in the cortex, both control and FST values were significantly reduced in fluoxetine-treated rats. In contrast to untreated rats, no increase in hippocampal 5-HT1A receptor mRNA was observed in response to FST in rats chronically treated with fluoxetine. Metabolism of 5-HT (5-HIAA/5-HT) in the brainstem was significantly decreased by fluoxetine and further reduced by swim stress, showing a certain degree of independence of these changes on 5-HT1A receptor gene expression that was increased in this brain region only after the FST, but not after fluoxetine. FST exposure also decreased the brainstem dopamine metabolism, which was unexpectedly positively correlated with 5-HT1A receptor mRNA levels in the frontal cortex. Together, these data suggest that the effects of the forced swim stress as well as fluoxetine involve brain region-dependent alterations in 5-HT1A receptor gene transcription, some of which may be interrelated with concomitant changes in catecholamine metabolism.

Plasma catecholamine and nephrine responses to brief intermittent maximal intensity exercise

Catecholamines (noradrenaline, NA; adrenaline, AD; dopamine, DA) influence the metabolic and cardiovascular responses to exercise. However, changes in catecholamine metabolism during exercise are unclear. Plasma normetanephrine (NMET), metanephrine (MET) and catecholamine responses to a laboratory-based model of games-type exercise were examined. Twelve healthy men completed a resting control trial and a trial consisting of ten 6 s cycle ergometer sprints interspersed with 30 s recovery, in randomised order. Resting and post-sprint venous blood samples were taken. Plasma NA and AD increased after each sprint but DA was unaltered. Plasma nephrines increased significantly from sprint 4 onwards with peak NMET increasing 60% to 0.76 +/- 0.19 nmol l(-1) and MET 230% to 0.37 +/- 0.16 nmol l(-1) from resting values (P < 0.05). The results demonstrate increased catecholamine metabolism via elevated catechol-O-methyl transferase activity during intermittent sprinting. The results may aid regulation of the metabolic and cardiovascular responses to exercise by maintaining tissue adrenoceptor sensitivity to circulating catecholamines.

Changes in catecholamine metabolism by ascorbic acid deficiency in spontaneously hypertensive rats unable to synthesize ascorbic acid

We have previously reported the establishment of a novel rat strain, SHR-od, with both spontaneous hypertension and a defect of ascorbic acid biosynthesis. Blood pressure in mature SHR-od fed an ascorbic acid-supplemented diet is over 190–200 mmHg, while it decreased to around 120 mmHg at 4–5 weeks after the cessation of ascorbic acid supplementation. With regard to possible mechanisms of blood pressure lowering, we focused on catecholamine synthesis in adrenal glands, since catecholamine is a major factor for blood pressure regulation and ascorbic acid is a co-factor of dopamine β-hydroxylase (DBH) in catecholamine biosynthesis. Male SHR-od (25-week-old) and normotensive ODS rats with a defect in ascorbic acid biosynthesis (25-week-old) were fed a Funabashi-SP diet with or without ascorbic acid (300 mg/kg diet) for 28 days or 35 days. In SHR-od, systolic blood pressure (191 ± 6 mmHg) began to decrease from day 21 in the ascorbic acid-deficient group, whereas no significant difference was found in ODS rats. In spite of significant lowering of blood pressure, no significant differences were found in catecholamine levels in serum, adrenal glands and brain on day 28. On day 35, however, urinary excretion of norepinephrine and epinephrine in the ascorbic acid-deficient SHR-od were higher at 490% ( P < 0.05) and 460% ( P < 0.05) of the respective control. Serum catecholamine concentrations and the adrenal catecholamine content tended to be higher in the ascorbic acid-deficient SHR-od than the control of SHR-od and reached to similar level in ODS rats. The administration of ascorbic acid (intraperitoneal injection, 60 mg ascorbic acid/kg body weight, once a day) to the ascorbic acid-deficient SHR-od restored blood pressure to the range 180–190 mmHg within two days. These findings indicate that ascorbic acid deficiency affects catecholamine metabolism in the adrenal glands of SHR-od in response to blood pressure lowering, suggesting catecholamines are not involved in the mechanism for the remarkable reduction in blood pressure in response to ascorbic acid deficiency.

Influences of Catecholamine Contents on Tetrahydrobiopterin Metabolism

Summary The influence of changes in catecholamine metabolism on tetrahydrobiopterin biosynthesis was investigated in cultured rat pheochromocytoma PC12 cells. The increase in the cellular dopamine content after treatment with the MAO-COMT inhibitor or dopamine produced decreases in the GTP-cy-clohydrolase I (GTPCH-I) activity and total biopterin content. On the contrary, the catecholamine increase after treatment with nerve growth factor produced increases in the GTPCH -I activity and total biopterin content. On the other hand, the decrease in the dopamine content after tyrosine hydroxylase (TH) inhibitor treatment produced decreases in the GTPCH-I activity and total biopterin content, but the catecholamine decrease (the DOPA content increased about 3.4-fold) after aromatic L-amino acid decarboxylase inhibitor treatment produced a decrease in the GTPCH-I activity. These results suggest that an increase in dopamine content that is not directly related to the action of TH plays a role in down-regulation of tetrahydrobiopterin biosynthesis and that when the changes in catecholamine metabolism are strongly associated with the action of TH, tetrahydrobiopterin biosynthesis is regulated depending on the necessity for TH.

Alteration of Catecholamine Phenotype in Transgenic Mice Influences Expression of Adrenergic Receptor Subtypes

Agonist-induced regulation of adrenergic receptors (ARs) has an important role in controlling physiological functions in response to changes in catecholamine stimulation. We previously generated transgenic mice expressing phenylethanolamine N-methyltransferase (PNMT) under the control of a human dopamine beta-hydroxylase gene promoter to switch catecholamine specificity from the norepinephrine phenotype to the epinephrine phenotype. In the present study, we first examined changes in catecholamine metabolism in peripheral tissues innervated by sympathetic neurons of the transgenic mice. In the transgenic target tissues, a high-level expression of PNMT led to a dramatic increase in the epinephrine levels, whereas the norepinephrine levels were decreased to 48.6-87.9% of the nontransgenic control levels. Analysis of plasma catecholamines in adrenalectomized mice showed large amounts of epinephrine derived from sympathetic neurons in the transgenic mice. Subsequently, we performed radioligand binding assays with (-)-[125I]iodocyanopindolol to determine changes in binding sites of beta-AR subtypes. In transgenic mice, the number of beta 2-AR binding sites was 56.4-74.9% of their nontransgenic values in the lung, spleen, submaxillary gland, and kidney, whereas the beta 1-AR binding sites were regulated in a different fashion among these tissues. Moreover, northern blot analysis of total RNA from the lung tissues showed that down-regulation of beta 2 binding sites was accompanied by a significant decrease in steady-state levels of the receptor mRNA. These results strongly suggest that alteration of catecholamine specificity in the transgenic sympathetic neurons leads to regulated expression of the beta-AR subtypes in their target tissues.

Possible Involvement of Hypothalamic Monoamines in Mediating the Action of Alpha-2u-Globulin on the Pituitary-Testicular Axis in Rats

A major androgen-dependent urinary protein of male rodents, alpha 2u-globulin, has been shown to influence adenohypophyseal hormone release. In an attempt to elucidate the mechanisms of its action, we have examined several parameters of hypothalamic and pituitary function in adult male rats treated for 2 weeks with two injections daily of 0.75 mg alpha 2u-globulin and sacrificed 16 h after the last injection. This treatment led to an increase in plasma luteinizing hormone levels, a decrease in plasma prolactin levels, an increase in testosterone concentrations in both plasma and testicular tissue, and increases in testicular weights. The norepinephrine turnover in median eminence and anterior hypothalamus was increased in alpha 2u-globulin-injected animals, while the norepinephrine turnover in the remaining medial basal hypothalamus was reduced. alpha 2u-Globulin-treated animals had a significantly decreased dopamine turnover in the anterior hypothalamus, while in the medial basal hypothalamus the dopamine metabolism was increased. These data suggest that alpha 2u-globulin-induced changes in gonadotropin and prolactin secretion are mediated by changes in catecholamine metabolism in several hypothalamic regions. Increased testosterone secretion appears to be due to increased secretion of gonadotropins from the pituitary.

Changes in catecholamine metabolism in the rostral ventrolateral medulla following halothane and nitroprusside-induced hypotension: an in vivo electrochemical study

The objective was to observe changes in rostral ventrolateral medulla (RVLM) catecholamine metabolism using in vivo voltammetry following induced hypotension with halothane or nitroprusside (SNP). Rats anesthetized (halothane, metocurine) and ventilated were stereotaxically implanted with carbon microelectrodes in the RVLM. The catechol oxidation current (CA·OC, % baseline) was used as an index of RVLM catecholaminergic metabolism. Groups of rats (n = 5) were given (A) halothane 0.75% for 60 min; (B) halothane 2.75% plus phenylephrine infusion to maintain mean arterial pressure (MAP) for 30 min, then halothane 0.75% for 30 min; (C) halothane (2.5–3.0%) for 30 min (MAP60 ± 5mmHg) then halothane 0.75% for 30 min; (D)halothane 0.75% and sodium nitroprusside (SNP) for 30 min (MAP60 ± 5mmHg), then halothane 0.75% for 30 min. Halothane 0.75% produced no significant change in CA·OC or MAP (A), while halothane 2.5–3.0% produced a significant decrease in MAP and a symmetrical significant increase in CA·OC (ANOVA,P < 0.5). This increase peaked at 30 min (180 ± 28%) and reached110 ± 9% baseline at 60 min. The halothane and phenylephrine combination produced no significant change in CA·OC or MAP during the 30 min exposure (B). SNP (D) produced a significant increase in CA·OC (peak 48 min,224 ± 35%) which remained elevated at 60 min (198 ± 32%). Thus, the induced hypotension produced activation of RVLM catecholaminergic neurons. SNP induced a prolonged significant increase in RVLM catecholamine metabolism which may relate to rebound hypertension following use of this drug.

Sex- and age-related changes in catecholamine metabolism and release of rat adrenal gland

To examine the possible existence of changes in the adrenal catecholaminergic activity during aging, we analyzed the adrenal content of catecholamines (CA) and the activities of selected enzymes involved in their metabolism as well as the basal and the K +-stimulated release of these CA in incubated adrenal tissue of aged (>22 months) and young (2 months) rats of both sexes. Adrenal contents of norepinephrine (NE) and epinephrine (E) of male rats were unaltered in aging, although aged males showed an increased activity of tyrosine hydroxylase (TH) and a decrease in phenylethanolamine-N-methyl transferase (PNMT) activity. In addition, the in vitro release of both CA as well as their content in the incubated adrenal tissue were higher in aged males than in young animals. However, the response of the adrenal of aged males to incubation with stimulatory concentrations of K + was significantly lower than that observed in young males. Aged females showed increases in the adrenal content of E, although the activities of TH and PNMT were unaltered. As in aged males, the in vitro release of CA from incubated adrenal tissue was higher in aged females than in young rats, but the CA amounts measured in the incubated tissues were similar. Moreover, the response to stimulatory concentrations of K + was lower in aged females than in young animals. In summary, these results clearly indicate that adrenal catecholaminergic activity is enhanced during aging, which could have important consequences for physiological functions regulated by the adrenal secretion. Also, some differences in the effects of aging could be observed between males and females.

Modulation of catecholamine metabolism in synaptosomes by a neuroregulatory factor from mammalian brain.

Incubation of synaptosomes from rat brain with bovine brain extract caused inhibition of oxidative deamination of dopamine, decreased formation of 3,4-dihydroxyphenylacetic acid, increased formation of norepinephrine and its N-methyl derivatives and increased release of catecholamines. Omission of Ca2+ from the extrasynaptosomal medium completely blocked the brain extract induced release of [3H]catecholamines and decreased, by about 80%, the effect on changes in catecholamine metabolism. Chromatography of the brain extract on Sephadex-G25 columns resulted in an active compound eluting at the position expected for compounds with molecular weights in the region of 1500 to 2500 Da.

Effects of dl‐2‐Amino‐5‐Phosphonovalerate on Metabolism of Catecholamines in Synaptosomes from Rat Brain

Incubation of synaptosomes from rat brain with DL-2-amino-5-phosphonovalerate (APV) stimulated an increased release of dopamine, and this effect was strictly dependent on the extrasynaptosomal calcium level. APV increased biosynthesis of dopamine from tyrosine by 30%, whereas monoamine oxidase activity was inhibited by 30%. When synaptosomes were incubated with radioactive dopamine, APV caused a large decrease in incorporation of label into 3,4-dihydroxyphenylacetic acid but greatly increased incorporation into norepinephrine and its N-methyl derivatives. Quantification of dopamine and its metabolites in synaptosomes, using electrochemical detection, indicated that the presence of APV resulted in changes in the absolute levels of the aforementioned dopamine metabolites similar to the changes in radiolabel incorporation. Omission of Ca2+ from the extrasynaptosomal medium greatly diminished the APV-induced changes in catecholamine metabolism. The metabolic changes appear to largely result from an increased intrasynaptosomal Ca2+ level due to the APV-induced increase in calcium permeability of the plasma membrane.

Stress-related activation of cerebral dopaminergic systems.

The changes in dopamine catabolites in various regions of mouse brain have been studied following a variety of behavioral treatments. In confirmation of the results of many others, we find that treatments such as footshock or restraint result in a pronounced activation of dopaminergic systems in the prefrontal cortex, as determined by increases in the content of DOPAC (3,4-dihydroxyphenylacetic acid). However, we also find small but statistically significant increases of DOPAC in the hypothalamus and brain stem even with mild treatments. With restraint and more intense footshock we observe increases of DOPAC in all regions studied, including nucleus accumbens, olfactory tubercle, amygdala, and the striatum. Thus in contrast to previous reports, we find that the DA response in stress is global like that of norepinephrine [as determined by increases of 3-methoxy,4-hydroxyphenylethyleneglycol, (MHPG)], and not specific to the prefrontal cortex. The activation of prefrontal cortex DA metabolism is associated with an activation of the synthetic enzyme tyrosine hydroxylase. The response pattern of catecholamine metabolites is similar following a variety of stressors, including conditioned footshock, training with one footshock in passive avoidance behavior, performance of passive avoidance behavior, and even following exposure to an apparatus in which mice have been shocked previously. Injection of mice with Newcastle disease virus increases plasma corticosterone, and DOPAC and MHPG in the hypothalamus and brain stem, but not the prefrontal cortex. Thus a virus infection can be considered a stressor. Furthermore, intracerebroventricular (ICV) injection of corticotropin-releasing factor (CRF) produces stresslike increases in DOPAC and MHPG concentrations, suggesting that the release of CRF in the brain during stress may mediate the changes in catecholamine metabolism.

Studies on the acute and long-term changes in dopamine and noradrenaline metabolism in mouse brain following administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Previous studies from these laboratories have revealed that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced acute profound release of dopamine together with a marked reduction in dopamine synthesis. The present study was undertaken in an attempt to further elucidate these acute alterations. MPTP produced dose-dependent marked reductions in the concentrations of dopamine and noradrenaline in mouse brain 2 hours as well as 7 days after the administration. Both the acute and long-term reductions in dopamine were most pronounced in the striatum, whereas the reductions in noradrenaline (acute and long-term) were most pronounced in the cortical region. Contemporaneous with the acute reduction in the catecholamines, MPTP increased the levels of the dopamine metabolites 3-methoxytyramine and homovanillic acid (HVA), and the noradrenaline metabolite normetanephrine. In contrast, the levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were reduced. These data are indicative of a profound release of both dopamine and noradrenaline from the storage sites into the extraneuronal space. Pretreatment with the monoamine oxidase inhibitor pargyline totally prevented the acute reduction in dopamine and partially also the reduction in noradrenaline produced by MPTP. However, MPTP increased the levels of 3-methoxytyramine and normetanephrine also in pargyline treated mice. The selective dopamine uptake inhibitor GBR 13098 antagonized the MPTP-induced reduction in dopamine and increase in 3-methoxytyramine, but had no effect on the MPTP-induced reduction in noradrenaline. MPTP produced a marked acute reduction in tyrosine hydroxylation in the dopamine predominated areas striatum and limbic region, whereas a slight increase in tyrosine hydroxylation was noted in the noradrenaline predominated cortical region. Similar effects of MPTP were observed in reserpine pretreated animals. Pargyline prevented the MPTP-induced reduction in dopamine synthesis. Recent in vitro observations indicate that MPP+, the toxic metabolite of MPTP, is capable of inhibiting the electron-transport carrier, an action which may account for the neurotoxicity of the compound. It appears possible that this effect of MPP+ could explain the currently observed acute changes in catecholamine metabolism.

Hyperprolactinemia disrupts neuroendocrine responses of male rats to female conspecifics.

An increase in plasma luteinizing hormone levels which occurs in the male rat in response to the presence of a receptive female was associated with increased norepinephrine metabolism in several regions of the hypothalamus and reduced norepinephrine metabolism in preoptic area and olfactory bulbs. Hyperprolactinemia induced by grafting three anterior pituitary glands beneath the kidney capsule blocked female-induced changes in norepinephrine metabolism and attenuated the increase in luteinizing hormone release. These results suggest that endocrine and behavioral responses of male rats to the presence of a female are mediated by changes in catecholamine metabolism in several brain regions. The ability of hyperprolactinemia to induce deficits in male sexual behavior may be due to the blockade of these CNS responses to exteroceptive stimuli originating from the female.

Effects of intraventricular injections of 6-hydroxydopamine on amine metabolites in rat brain and urine

The effects in rats of intraventricular injections of 6-hydroxydopamine (6-OHDA) on the urinary excretion 1–3 weeks later of 3-methoxy-4-hydroxyphenethylene glycol (MHPG), 3,4-dihydroxyphenethanol (DHPE), 3-methoxy-4-hydroxyphenethanol (MHPE), p-hydroxyphenylglycol (pHPG), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were examined. The excretion of MHPG was decreased to 63 and 71% of control on days 7 and 14, respectively, but had returned to control levels by day 23, even though the brain levels were decreased by 87%. Free and total HVA excretion was reduced on both days 7 and 23, but free and total DOPAC was reduced only on day 7. Based on these data, it can be estimated that about 39% of the free and 46% of the total HVA in urine originates in the CNS. The excretion of conjugated HVA was decreased by 70–80%, but this decrease does not support the notion that the conjugated form of HVA is derived principally from the brain and thus serves as a better marker of brain dopamine metabolism, since the level of this metabolite in the brain was not correspondingly decreased but was instead increased. Urinary DOPAC levels were generally more variable and derived to a greater extent from the periphery; therefore, DOPAC appears to be less suitable than HVA as a marker of brain dopamine. The results also indicate that as much as 35% of the urinary MHPG may originate in the CNS, although compensatory changes in catecholamine metabolism in either the brain or in the periphery may have somewhat influenced this estimate. The results also suggest that at least as much pHPG as MHPG in urine derives from the CNS. The data are consistent with the idea that the neutral dopamine metabolites largely derive from the brain, but the relatively small depletion in their brain levels produced by 6-OHDA prevented the exact proportion being determined accurately.

Effect of Middle Cerebral Artery Occlusion on Serotonin Metabolism in Rat Brain

Previously the authors have studied local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) in rats 1 hour after the occlusion of the left middle cerebral artery. It was found that LCGU was decreased in the ipsilateral cerebral cortex and the lateral striatum, where LCBF was also reduced. On the other hand, LCGU was increased in the ipsilateral medial striatum, olfactory tubercle, globus pallidus, subthalamic nucleus, and lateral habenula. They have also investigated changes in catecholamine metabolism in these regions and found very close relationship between LCGU, LCBF, and dopamine metabolism. In the present work, changes in serotonin metabolism were investigated measuring tryptophan (TRP), serotonin (5-hydroxytryptamine, 5-HT), and its metabolite, 5-hydroxy-indoleacetic acid (5-HIAA) in certain regions of the cerebral cortex, basal ganglia, and brain stem using the same ischemic model rats. The results were compared with the changes in LCGU and LCBF. The concentration of TRP was significantly increased in the “ischemic” regions, such as the ipsilateral cerebral cortex and lateral striatum. On the other hand, 5-HT was significantly decreased not only in the “ischemic” regions but also in the “nonischemic” regions such as the globus pallidus. There was a tendency for 5-HT to decrease in the ipsilateral substantia nigra and raphe nuclei. 5-HIAA showed no significant change in the “ischemic” regions but was significantly increased in the globus pallidus and raphe nuclei and had a tendency to increase in the substantia nigra. There was no significant change in any of these parameters in the regions of the contralateral side. The changes in 5-HT metabolism in the “ischemic” regions, such as the ipsilateral cortex and lateral striatum indicate that the synthesis of 5-HT was reduced, but its release was unchanged. Increase in 5-HT metabolism in the “nonischemic” regions, such as the globus pallidus, substantia nigra, and raphe nuclei indicates a presence of neuronally-mediated biochemical diaschisis.

Noradrenergic modulation of neuronal transmission in the offspring of amphetamine-treated rats.

The model of noradrenergic modulation of synaptic transmission between the entorhinal cortex and dentate gyrus was used to investigate the function of catecholaminergic neurones in the offspring of rats injected with dl-amphetamine during pregnancy (0.5 mg . kg-1 . day-1; s.c.). A conditioning train of pulses applied to the locus coeruleus produces an increase in the amplitude of the population spike evoked in the granule layer of the gyrus dentatus by perforant path stimulation. Results show that, in the offspring of amphetamine-treated rats, the potentiating effect of locus coeruleus stimulation was two to three times greater than in control animals (151 +/- 30 vs. 66 +/- 20%; p less than 0.05). This effect may be due to the changes in catecholamine metabolism and (or) catecholamine receptors observed in these animals and could help explain the behavioral alterations caused by amphetamine exposure in utero.

Increase in histamine concentrations in discrete hypothalamic nuclei of spontaneously hypertensive rats

Histamine meets many of the criteria which must be satisfied in order to consider a compound as a neurotransmitter in the central nervous system (CNS). It is localized in synaptosomes after subcellular fractionation of brain tissue is. Discrete histaminergic pathways have been described in the brain 10. Endogenous histamine can be released from brain slices by depolarizing the nerve cells with potassium as. Iontophoresis of histamine modifies the action potentials of cerebral neurons 25. When injected intraventricularly 27 or directly into discrete brain areas 12, histamine has potent effects on neuronal activity. In addition, histamine receptors 7 and a histamine-sensitive adenylate cyclase la have recently been characterized in the brain. Pharmacological evidence indicates that histamine has centrally mediated effects on blood pressure2,14,as, 37. These observations suggest that endogenous brain histamine could play a role in the regulation of blood pressure or in the pathogenesis of hypertension. Selective changes in catecholamine metabolism, discretely localized to a few nuclei and areas of the brain, had been found in several models of hypertension 2s-a0. A similar situation could be envisioned for other putative neurotransmitters such as histamine. We have attempted the quantitation of endogenous histamine levels in those discrete brain areas which are part of the principal central pathways regulating cardiovascular functions in mammals. The study was conducted at two stages of the development of the genetic hypertension using young (4 weeks old) and adult (12 weeks old) spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats, WKY)ZL These ages were selected for their difference in manifested high blood pressure and because there are age-specific changes in catecholamine metabolism in similar brain structures29, so.

Effect of scurvy on reserpine induced hypothermia in the guinea pig

Resting body temperatures of scorbutic guinea pigs were significantly higher when compared to control animals. Following the injection of reserpine (5 mg/kg, ip) body temperatures of control and scorbutic animals fell, but at 24 h scorbutic animals came to lower body temperatures. The determination of catecholamines in the heart, adrenal glands, and brain revealed significant changes in the steady-state levels of these amines. This evidence supports the hypothesis that changes in catecholamine metabolism occur which are reflected in the regulation of resting body temperature and the ability of scorbutic guinea pigs to control body temperature during reserpine induced hypothermia.