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PubMed1982

Studied on cerebellar haem metabolism in the rat in vivo.

Rats were injected intraventricularly with 5-amino[4-14C]laevulinate and the radioactivity recovered in the total cerebellum homogenate and in its haem and porphyrin fractions was determined in time. Two phases could be distinguished in the decline of haem radioactivity, suggesting labelling of at least two pools of widely different turnover rates. Succinyl acetone, when injected intraventricularly, caused a marked and long-lasting inhibition of cerebellar 5-aminolaevulinate dehydratase activity and a corresponding inhibition of the incorporation of [14C]5-aminolaevulinate into cerebellar haem in vivo. Inhibition of cerebellar haem biosynthesis by succinylacetone was followed by stimulation of the first enzyme of the pathway, 5-aminolaevulinate synthase, whereas intraventricular injection of haematin led to a significant depression of the activity of the enzyme. This suggested that the cerebellar 5-aminolaevulinate synthetase is regulated by haem through a negative feedback mechanism. Rats given repeated doses of succinylacetone, so as to maintain 80% inhibition of their cerebellar 5-aminolaevulinate dehydratase activity for 5 days, failed to exhibit any obvious symptoms of toxicity but became more sensitive to the neurotoxic effects of large intraventricular doses of 5-aminolaevulinate.

5-Aminolevulinate Synthetase↗

PubMed1988

Osmoreceptor mechanism for oxytocin release in the rat.

In order to determine whether oxytocin release is controlled by an osmoreceptor mechanism identical with that for vasopressin release, the plasma oxytocin concentration and plasma osmolality were measured during intraatrial infusion and after intraventricular injection of various osmotic solutions in unanesthetized rats. Intraatrial infusion of 0.6 M NaCl Locke solution (L.S.) or 1.2 M mannitol L.S. elevated plasma oxytocin significantly, while 1.2 M urea L.S. caused only a small increase and isotonic L.S. did not change in plasma oxytocin. All hypertonic solutions produced significant and similar increases in the plasma osmolality. Plasma oxytocin was positively correlated with plasma osmolality in the animals infused with hypertonic NaCl or mannitol but not in the animals infused with hypertonic urea. The injection of 2 microliters of 0.6 M NaCl artificial cerebrospinal fluid (CSF) or 1.2 M mannitol CSF into the third ventricle caused a significant increase in plasma oxytocin immediately (5 min after injection) without changing plasma osmolality, while the intraventricular injection of 1.2 M urea CSF or isotonic CSF produced no significant change in plasma oxytocin. These results indicate that oxytocin release is controlled by osmoreceptors rather than Na receptors, that the adequate stimulus for the osmoreceptors is one which produces cellular dehydration and that the osmoreceptors are located in the brain region which is accessible to osmotic agents from both the outside and inside of the blood-brain barrier. Since the organum vasculosum of the lamina terminalis (OVLT) lacks a blood-brain barrier and is known to be involved in osmotic control of vasopressin release, a lesion was made in the anteroventral region of the third ventricle which encompasses the OVLT and the effect of hypertonic NaCl infusion on oxytocin release was examined. No significant increase in plasma oxytocin was observed after intraatrial infusion of 0.6 M NaCl L.S. in the lesioned rats. All of these findings lead to the conclusion that oxytocin release is under the control of osmoreceptors identical to those for vasopressin release.

Animals↗

PubMed1980

Thymidine transport in the central nervous system.

The mechanisms by which thymidine enters and leaves brain, choroid plexus, and CSF were investigated by injecting [3H]thymidine intravenously and intraventricularly. [3H]thymidine, with and without unlabeled thymidine, was infused at a constant rate into conscious adult rabbits. At 150 min, [3H]thymidine readily entered CSF, choroid plexus, and brain. In brain, approximately 45% of the nonvolatile radioactivity was [3H]thymidine phosphates. The addition of 0.21 mmol/kg unlabeled thymidine to the infusion syringe decreased the phosphorylation of [3H]thymidine in brain by approximately 85%; the addition of 2.1 mmol/kg of unlabeled thymidine to the infusion syringe decreased the relative entry of [3H]thymidine into CSF and brain by 40 and 78%, respectively. Two h after intraventricular injection of [3H]thymidine, [3H]thymidine was rapidly cleared from CSF, in part, to brain, where approximately 40% of the [3H]thymidine was converted to [3H]thymidine phosphates. The intraventricular injection of unlabeled thymidine (21 mumol) with the [3H]thymidine abolished the phosphorylation of [3H]thymidine in brain and significantly decreased the clearance of [3H]thymidine from the CSF. Rabbit brain slices accumulated [3H]thymidine by an energy-dependent, saturable high-affinity system that depended, in part, on intracellular phosphorylation of the [3H]thymidine. These results were interpreted as showing that the entry of thymidine from blood into CSF and presumably the extracellular space of brain and then into brain cells involves one or more saturable transport and/or metabolic steps.

Animals↗

PubMed1991

Cerebral ischemia decreases the behavioral effects and mortality rate elicited by activation of NMDA receptors in mice.

The purpose of this study was to determine whether prior transient cerebral ischemia, in conscious mice, would alter the biological responses resulting from excessive activation of N-methyl-D-aspartate (NMDA) receptors, in an early stage. The responses to the activation of NMDA receptors by an intracerebroventricular injection of NMDA, such as wild running, tonic and clonic convulsions, absence of the visual placing reflex, loss of the righting reflex, impaired motor function and a high mortality rate, were to a large extent prevented if 30 min before treatment, either a 10-min period of global cerebral ischemia was induced or a 1 nmol intraventricular injection of NMDA was given but not if either of the above procedures was done one day before the test dose of NMDA. In contrast, behavioral symptoms, in response to activation of non-NMDA-type glutamate receptors elicited by intraventricular injection of either kainic acid or AMPA, were not clearly affected. Transient systemic hypercapnic anoxia (22-sec exposure to 100% CO2 gas), before treatment with NMDA did not significantly reduce the NMDA-induced behavior. The severity of these behavioral responses and high mortality rate observed after intraventricular injection of pentylenetetrazole (PTZ, 30 mumol) were not altered by either prior global ischemic insult or by a preexposure to NMDA given intraventricularly. The NMDA antagonist, MK801 (0.1 and 0.3 mg/kg i.p.) greatly reduced the behavioral effects and mortality rate, resulting from the intraventricular injection of NMDA and somewhat reduced the effects of the intraventricular injection of PTZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of blockade of AT1 and AT2 receptors in brain on the central angiotensin II pressor response in conscious spontaneously hypertensive rats.

Intracerebroventricular (i.c.v.) administration of angiotensin II (ANG II) increases vascular resistance and arterial pressure by increasing the activity in the sympathetic nervous system (SNS-component) and secretion of vasopressin (VP-component). This study examined the role of AT1 and AT2 receptors in brain in mediating the exaggerated central cardiovascular effects of ANG II in conscious, adult (10 weeks) spontaneously hypertensive rats (SHR). Mean arterial pressure, heart rate and renal blood flow responses to intraventricular injection of ANG II (100 ng in 5 microliters) were determined 10 min after intraventricular administration of the AT1 receptor antagonist losartan alone (1.0, 2.5, 5.0, 10.0 micrograms), the AT2 receptor ligand PD 123319 alone (3.5 x [10(-6), 10(-4), 10(-2), 10(0)] micrograms), or both ligands in combination. In control rats, intraventricular administration of losartan prevented the pressor and renal vascular resistance responses to intraventricular injection of ANG II, in a dose-dependent manner (P < 0.05), while intraventricular injection of PD 123319 was ineffective. Likewise, when the SNS- and VP-components were studied individually by preventing the VP-component with a V1 receptor antagonist (i.v.) or the SNS-component with chlorisondamine (i.v.), losartan (i.c.v.) prevented both components, while PD 123319 (i.c.v.) was without affect. In addition, doses of losartan, combined with 3.5 micrograms PD 123319, were no more effective in preventing the pressor or renal vascular resistance responses than losartan, administered alone, suggesting that the VP- and SNS-components of the pressor response to ANG II (i.c.v.) are mediated primarily by AT1 receptors in brain in conscious spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1977

The effects of reserpine and 6-hydroxydopamine on the concentrations of some arylakylamines in rat brain.

1 The concentrations of p- and m-tyramine were measured in the caudate nucleus of the rat brain following subcutaneous injection of reserpine or intraventricular injection of 6-hydroxydopamine, beta-Phenylethylamine was analysed in the hypothalamus after reserpine. 2 Endogenous levels of p-tyramine and m-tyramine in the caudate nucleus, and beta-phenylethylamine in the hypothalamus were 8.02, 2.25 and 2.52 ng/g respectively. 3 Tyramine concentrations were reduced to less than 20% of control values one day after a reserpine injection of 1 or 10 mg/kg. A single dose of reserpine (0.4 mg/kg) significantly decreased the content of both tyramines in the caudate nucleus. The effects became apparent as early as 45 min after drug case of m-tyramine. 4 The hypothalamic content of beta-phenylethylamine was unaffected by reserpine. 5 Ten days after an intraventricular injection of 6-hydroxydopamine (250 mug), p- and m-tyramine concentrations in the caudate nucleus were significantly below control levels. 6 The results suggest that p- and m-tyramine may be stored by an intraneuronal reserpine-sensitive storage mechanism. Alternatively, the tyramines may replace some of the catecholamines from their storage granules and then be released as false transmitters by the nervous impulse. The observed changes in tyramine levels might also the fact that these amines may be metabolically related to another amine which is stored in reserpine-sensitive granules.

Animals↗

PubMed1976

Intraventricular anti-cholinergics do not block cholinergic hippocampal RSA or neocortical desynchronization in the rabbit or rat.

Electroencephalographic (EEG) electrodes and ventricular cannulae were implanted in 8 rabbits and 12 rats. Two anti-cholinergic agents, atropine sulfate and scopolamine hydrobromide, were given systemically (1-50 mg/kg) and intraventricularly (5-800 mug). Systemic but not intraventricular injections blocked sensory stimulation-induced or eserine-induced neocortical desynchronization and hippocampal RSA in rats and rabbits which were immobile and either undrugged or ethanol intoxicated. Systemic injections also blocked hippocampal RSA but not neocortical desynchronization in rats given sensory stimulation under urethane anaesthesia, while intraventricular injections only reduced RSA amplitude. Neither systemic nor intraventricular injections blocked neocortical desynchronization or hippocampal RSA recorded from animals when they walked in a motor driven wheel. These experiments support the hypothesis that there are two types of neocortical desynchronization and hippocampal RSA, one cholinergic and one non-cholinergic. They also suggest that atropine and scopolamine pass more readily to the neural system responsible for cholinergic EEG activity from the capillary bed than from the ventricular fluid.

Animals↗

PubMed1972

The hyperglycaemic effect of morphine.

1. In the unanaesthetized cat, an injection of 0.75 mg of morphine into a lateral cerebral ventricle produced strong hyperglycaemia; on intravenous injection, 10 to 30 times larger doses were required. Other effects produced with both injections were shivering, pupillary dilatation, opening of the eyes, miaowing, periods of excitation, and analgesia. Between the periods of excitation the cat did not react to objects moving in front of its eyes and it had a vacant stare.2. Noradrenaline, adrenaline, and 5-hydroxytryptamine (5-HT) injected intraventricularly (250 mug, twice) depressed the hyperglycaemia due to intraventricular morphine, and noradrenaline also depressed the hyperglycaemia due to intravenous morphine. Adrenaline produced the strongest and 5-HT the weakest depression. 5-HT did not depress the other effects of morphine, but the catecholamines depressed most of them; only analgesia and the vacant stare appeared to be unaffected.3. Reserpine injected intraventricularly (0.5 mg, twice) greatly accentuated the hyperglycaemia as well as the other effects produced by intraventricular morphine, but pupillary dilatation and opening of the eyes no longer occurred; the protrusion of the nictitating membranes produced by the reserpine persisted.4. Pentobarbitone sodium injected intraperitoneally in an anaesthetizing dose practically abolished the morphine hyperglycaemia, but injected intraventricularly in a dose of a few milligrammes, it had a two fold effect: depression followed by enhancement of the morphine hyperglycaemia. The enhancement may be due to sensitization of the effect of the adrenaline released by morphine, since adrenaline hyperglycaemia was enhanced as well.5. Morphine did not seem to act on structures in the walls of either the lateral or third ventricle when producing its hyperglycaemic effect on intraventricular injection. The action may therefore be on more caudally situated parts of the neuro-axis, on the central grey, on structures in the floor of the fourth ventricle or of the lateral recesses, or even on structures near the ventral surface of the brain stem.

Analgesia↗

PubMed1974

Hyperglycaemia produced by the polyamines spermine and spermidine.

1 Intravenous injection of rabbits with the polyamines spermine (10-30 mg/kg) and spermidine (50-90 mg/kg) produced hyperglycaemia.2 Given by intraventricular injection, spermine and spermidine gave rise to hyperglycaemia in doses 250-500 times smaller than those effective intravenously.3 Intraventricular injections of the polyamines also produced hyperglycaemia in rats. Adrenal demedullation abolished the response.4 In the rabbit, the hyperglycaemia resulting from intraventricular injection of polyamines was abolished in reserpine-treated animals. Anaesthesia had no effect on the response unless accompanied by anoxia, when the response was potentiated.5 Intracisternal injections of the polyamines in rabbits were less effective than intraventricular injections in that doses about four times larger were required to elicit an equivalent response.

Animals↗

PubMed1977

6-hydroxydopamine destruction of central adrenergic neurones prevents or reverses developing DOCA-salt hypertension in rats.

The role of brain catecholaminergic neurones in the pathogenesis of DOCA-salt hypertension in the rat was investigated by selective depletion of central catecholamines using intraventricular or intracisternal administration of 6-hydroxydopamine (6-OHDA). Only the intraventricular injections prevented the development of hypertension. In addition, intraventricular 6-OHDA reversed the hypertension produced by two weeks but not six weeks of DOCA-salt treatment. The ability of intraventricular injections of 6-OHDA to prevent or reverse DOCA-salt hypertension while intracisternal injections do not, appears to be related to the greater depletion of brain catecholamines produced by the intraventricular injections. Only in the spinal cord and in the locus coeruleus were the norepinephrine contents depleted equally by either injection route. These findings suggest that central catecholaminergic neurones other than those originating in the locus coeruleus or descending in the spinal cord are important in the initiation, but not in the long term maintenance, of DOCA-salt hypertension. The influence of the central catecholamine neurons involved in the development of DOCA-salt hypertension might be mediated neurally via nonadrenergic pathways or hormonally via the brain-pituitary-endocrine system.

Adrenergic Fibers↗

PubMed1996

Altered NGF protein levels in different brain areas after immunolesion.

Nerve growth factor (NGF) provides critical trophic support to the cholinergic basal forebrain neurons that express high levels of the low-affinity NGF receptor (p75NGFR) in the adult rat brain. Intraventricular injection of 192 IgG-saporin, made by coupling the monoclonal antibody to p75NGFR 192 IgG to the cytotoxin saporin, selectively destroys the p75NGFR-bearing neurons in the basal forebrain and was used here to examine the effects of selective cholinergic lesions on brain NGF protein levels. We showed that 192 IgG-saporin produced significant long-lasting elevation of NGF protein levels in the hippocampus, cortex, and olfactory bulb, with profound reductions of ChAT activities representing complete cholinergic deafferentations of these areas. NGF level was maintained in the basal forebrain, even though there was almost complete loss of p75NGFR-immunoreactive cells and significant decrease of ChAT activity. In addition, a mild glial response was observed in the basal forebrain, and most of the activated astroglia expressed NGF-like immunoreactivity there. The increases in NGF protein levels in the target areas of the basal forebrain were most likely due to loss of cholinergic basal forebrain neurons and retrograde transport of NGF from these areas. Glial-derived NGF is partially responsible for the maintained level of NGF in the basal forebrain after the loss of cholinergic neurons. The accumulation of NGF protein in the target areas may have some effects on synaptic rearrangement in denervated tissues.

Animals↗

PubMed1985

Endocytic and exocytic pathways of the neuronal secretory process and trans-synaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo.

The lectin wheat germ agglutinin (WGA) conjugated to horseradish peroxidase (HRP) was employed to study the endocytic and exocytic pathways of the secretory process in neurons and the potential for trans-synaptic transfer of molecules within the CNS. WGA-HRP binds to surface membrane oligosaccharides and enters cells by adsorptive endocytosis. The lectin conjugate was administered intranasally or into the cerebral ventricles of mice; postinjection survival times ranged from 5 minutes to 6 days. Due to binding of the lectin to ependymal cells subsequent to an intraventricular injection, only select populations of neurons (i.e., hippocampal formation; paraventricular nuclei; midbrain raphe; VI, X, XII motor nuclei; among others) were exposed extracellularly to WGA-HRP and became labeled by retrograde axoplasmic transport from axon terminals or by direct cell body/dendritic uptake. WGA-HRP delivered intranasally was endocytosed by first-order olfactory neurons and transported by anterograde axoplasmic flow to the terminal field within the glomerular layer of the main olfactory bulb; eventually perikarya of the mitral cell layer were labeled, presumably by anterograde trans-synaptic transfer of the lectin conjugate. In the variety of neurons analyzed ultrastructurally following exposure to WGA-HRP, the proposed sequence of intracellular pathways through which peroxidase reaction product was traced over time was: cell surface membrane----endocytic structures----endosomes (presecondary lysosomes)----transfer vesicles----transmost Golgi saccule----vesicles, vacuoles, and/or dense core granules. WGA-HRP also labeled vesicles and tubules that were channeled to and/or derived from spherical endosomes, dense bodies, and multivesicular bodies. The peroxidase-positive, membrane-delimited products of the trans Golgi saccule contributed to anterograde axonal transport vectors and accumulated within axon terminals. A second contribution to these vectors was provided by peroxidase-labeled tubules and dense bodies believed to represent components of the lysosomal compartment. Profiles of the axonal reticulum comparable to those that stained cytochemically for glucose-6-phosphatase activity, a marker for the endoplasmic reticulum, were not associated with the transport of WGA-HRP. Trans-synaptic transfer of WGA-HRP from primary olfactory neurons to postsynaptic cells in the olfactory bulb was reflected in peroxidase-positive endocytic vesicles, endosomes, dense bodies, and the trans Golgi saccule.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intranasal↗

PubMed1991

Use of a digital brain atlas to compare the distribution of NGF- and bFGF-protected cholinergic neurons.

The effectiveness of basic fibroblast growth factor and nerve growth factor in preventing the lesion-induced disappearance of septal cholinergic neurons was compared by using a computerized data-acquisition system and a digital brain atlas that yielded quantitative and distributional information. Adult rats were given unilateral partial transections of the fimbria and then received daily intraventricular injection of one of the growth factors for 15 days. Given the high degree of co-localization of nerve growth factor receptors with choline acetyltransferase in these areas, cholinergic neurons were identified by nerve growth factor receptor immunoreactivity. Their locations were plotted in the context of a three-dimensional brain atlas permitting the analysis of relative distributions of cholinergic neurons in control brains and those of animals treated with each growth factor. The cholinergic cell disappearance induced by the partial fimbrial transection was restricted to the medial septal nucleus and the vertical limb of the diagonal band of Broca. Within the affected areas cholinergic cell disappearance increased gradually in severity from anterior to posterior levels of the septal nucleus. Both growth factors prevented the disappearance of cholinergic cell bodies in medial septal nucleus and vertical limb of the diagonal band. In lesioned control animals the unilateral cell disappearance amounted to 53.5% of the number of cholinergic neurons of the unlesioned side. Nerve growth factor and basic fibroblast growth factor reduced this disappearance to 13% and 28%, respectively. The distribution of cholinergic cells was the same in animal treated with each growth factor, suggesting that the two growth factors protect the same population of cholinergic neurons.

Brain↗

PubMed1992

Serotonin uptake by astrocytes in situ.

Co-localization of glial fibrillary acidic protein (GFAP) and radioactivity was examined after intraventricular injection of [3H]5-HT in adult rat brains. Radioactivity localized over GFAP-positive astrocytes was seen, especially when image-enhancing techniques were applied to the data. Also slices prepared from astrogliotic hippocampi of rats pretreated with kainic acid showed a twofold increased uptake of [3H]5-HT compared to control slices. This indicates that the uptake of [3H]5-HT seen in primary astrocyte cultures also occurs for astrocytes in situ. Also, as with astrocyte cultures, only some of the GFAP(+) astrocytes in situ showed localization of radioactivity, supporting the concept of intraregional heterogeneity of astrocyte functions.

Animals↗

PubMed2005

Angiotensin-converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6-hydroxydopamine rat model of Parkinsonism.

It is now established that the brain possesses a local renin-angiotensin system and that angiotensin II exerts multiple actions in the nervous system, including regulation of striatal dopamine release. Furthermore, angiotensin activates NADPH-dependent oxidases, which are a major source of superoxide, and angiotensin-converting enzyme inhibitors, commonly used in the treatment of hypertension and chronic heart failure, have shown antioxidant properties in several tissues. Oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. In the present study, we treated rats with intraventricular injections of the dopaminergic neurotoxin 6-hydroxydopamine and subcutaneous injections of the angiotensin-converting enzyme inhibitor Captopril to study the possible neuroprotective effect of the latter on the dopaminergic system and on 6-hydroxydopamine-induced oxidative stress. Rats treated with Captopril and 6-hydroxydopamine showed significantly less reduction in the number of dopaminergic neurons (i.e., immunoreactive to tyrosine hydroxylase) in the substantia nigra and in the density of striatal dopaminergic terminals than 6-hydroxydopamine-lesioned rats not treated with Captopril. In addition, Captopril reduced the levels of major oxidative stress indicators (i.e., lipid peroxidation and protein oxidation) in the ventral midbrain and the striatum of 6-hydroxydopamine-lesioned rats. Our results suggest that angiotensin-converting enzyme inhibitors may be useful for treatment of Parkinson's disease and that further investigation should focus on the neuroprotective capacity of these compounds.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1981

Effect of CDP-choline on the biosynthesis of phospholipids in brain regions during hypoxic treatment.

Acute administration of CDP-choline (i.p. 100 mg/Kg b.w.), 10 min before the intraventricular injection of labeled precursors, [2-3H] glycerol and [1-14C]-palmitate, was able to correct the impairment caused by hypoxic treatment of lipid metabolism in some brain regions, ie, cerebral hemispheres, cerebellum, and brainstem. After CDP-choline treatment, an increase of the specific radioactivity of total lipids and of phospholipids was observed in mitochondria purified from the three above-mentioned brain regions of the hypoxic animals, while no effect on the other subcellular fractions was found. CDP-Choline had a stimulating effect particularly on the incorporation of both precursors into mitochondrial PC, PE, and polyglycerophosphatides isolated form the three brain regions examined. The results obtained show that the action of CDP-choline in restoring lipid metabolism was more pronounced in brain mitochondria, which, among subcellular fractions, were the most affected by the hypoxic treatment.

Animals↗

PubMed1993

Changes of amino acid and monoamine levels after neonatal 6-hydroxydopamine denervation in rat basal ganglia, substantia nigra, and Raphe nuclei.

The effects of a neonatal dopaminergic deafferentation with the neurotoxin 6-hydroxydopamine (6-OHDA) on endogenous tissue levels of catecholamines, indoleamines, and amino acids were investigated in discrete rat brain regions. After producing the lesion at postnatal day 3 by intraventricular injections of 6-OHDA, with a desipramine pretreatment to protect noradrenaline neurons, the animals were kept for 3 months. Their brains were dissected to obtain samples of neostriatum, Globus pallidus, Substantia nigra, and Raphe nuclei, which were then analyzed by high-performance liquid chromatography, coupled either to electrochemical detection for aromatic monoamines, or to post-column ninhydrin derivatization with spectrophotometry for amino acids. The neonatal 6-OHDA treatment depleted dopamine (DA) levels in neostriatum, Globus pallidus, and Substantia nigra, but in Raphe nuclei DA was increased. The main metabolites of DA were also decreased in neostriatum, Globus pallidus, and Substantia nigra but remained unchanged in Raphe nuclei. Serotonin (5-HT) and its metabolite 5-hydroxy-indole-3-acetic acid increased in neostriatum and Raphe nuclei; in Substantia nigra there was a slight increase in 5-HT only. The 6-OHDA lesion caused heterogeneous alterations in amino acid contents, which varied according to the region. In the neostriatum there were increases of gamma-aminobutyric acid (GABA), aspartic acid, and glycine. In the Globus pallidus taurine, GABA, glutamic acid, glutamine, aspartic acid, serine, and alanine were elevated. In the Substantia nigra only increases in taurine, GABA, glutamic acid, and glutamine could be documented. This study shows important changes in amino acid levels and in some of their ratios, occurring in different anatomical subdivisions of the basal ganglia and related brainstem nuclei following a neonatal treatment with 6-OHDA. The results thus demonstrate major biochemical modifications in amino acids in the aftermath of a DA denervation and/or a 5-HT hyperinnervation during an early developmental period.

Amino Acids↗

PubMed2003

Role of epinephrine stimulation of CNS alpha1-adrenoceptors in motor activity in mice.

The role of brain epinephrine (EPI) in the regulation of motor activity and movement in mice was examined. Blockade of EPI synthesis with i.p. 2,3-dichloro-alpha-methylbenzylamine (DCMB) or LY134046 was found to produce marked behavioral inactivity which could be significantly reversed by intraventricular injection of EPI and by three other alpha(1)-adrenoceptor agonists, norepinephrine (NE), 6-fluoronorepinephrine (6FNE), and phenylephrine (PE), as well as by serotonin (5HT). EPI had the largest effect of these agonists and also was the only one that reversed nondrug-induced inactivity of mice in their home cages during the light phase. The effects of EPI were blocked by coinfusion of an alpha(1)-adrenoceptor antagonist (terazosin) but not of an alpha(2)-(atipamezole) or beta(1) (betaxolol)-blocker. The rank order of maximal behavioral responses to EPI, 6FNE, and PE in DCMB-treated mice was the same as the rank order of their maximal stimulation of hydrolysis of phosphatidylinositol at cloned alpha(1B)-adrenoceptors in cell culture. On the basis of the above findings and of the central distributions of adrenergic neurons and alpha(1)-adrenoceptors, the existence of a central EPI-innervated alpha(1)-adrenergic receptor system is postulated which serves to coexcite or enhance signaling in several monoaminergic brain regions involved in movement and motor activity.

Adrenergic alpha-Agonists↗