Corpus Striatum Of Rat Brain Research Articles

Role of dopaminergic receptors and post synaptic signaling in arsenic induced neurotoxicity: Ameliorative effect of curcumin

Objectives: In view of increasing incidences of arsenic induced dopaminergic alterations, study has been carried out to investigate protective role of curcumin in arsenic induced alterations in dopamine receptor and post synaptic signaling in corpus striatum of rat brain.

Silica nanoparticles mediated neuronal cell death in corpus striatum of rat brain: implication of mitochondrial, endoplasmic reticulum and oxidative stress

Extensive uses of silica nanoparticles (SiNPs) in biomedical and industrial fields have increased the risk of exposure, resulting concerns about their safety. We focussed on some of the safety aspects by studying neurobehavioural impairment, oxidative stress (OS), neurochemical and ultrastructural changes in corpus striatum (CS) of male Wistar rats exposed to 80-nm SiNPs. Moreover, its role in inducing mitochondrial and endoplasmic reticulum (ER) stress-mediated neuronal apoptosis was also investigated. The results demonstrated impairment in neurobehavioural indices, and a significant increase in lipid peroxide levels (LPO), hydrogen peroxide (H2O2), superoxide (O2 -) and protein carbonyl content, whereas there was a significant decrease in the activities of the enzymes, manganese superoxide dismutase (Mn SOD), glutathione peroxidase (GPx), catalase (CAT) and reduced glutathione (GSH) content, suggesting impaired antioxidant defence system. Protein (cytochrome c, Bcl-2, Bax, p53, caspase-3, caspase 12 and CHOP/Gadd153) and mRNA (Bcl-2, Bax, p53 and CHOP/Gadd153, cytochrome c) expression studies of mitochondrial and ER stress-related apoptotic factors suggested that both the cell organelles were involved in OS-mediated apoptosis in treated rat brain CS. Moreover, electron microscopic studies clearly showed mitochondrial and ER dysfunction. In conclusion, the result of the study suggested that subchronic SiNPs’ exposure has the potential to alter the behavioural activity and also to bring about changes in biochemical, neurochemical and ultrastructural profiles in CS region of rat brain. Furthermore, we also report SiNPs-induced apoptosis in CS, through mitochondrial and ER stress-mediated signalling.

Characterization of the norepinephrine-activation of adenylate cyclase suggests a role in memory affirmation pathways: Overexposure to epinephrine inactivates adenylate cyclase, a causal pathway for stress-pathologies

Incubation with noradrenaline (norepinephrine) of isolated membranes of rat's brain corpus striatum and cortex, showed that ionic-magnesium (Mg 2+) is required for the neurotransmitter activatory response of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing) (EC 4.6.1.1)], AC. An Mg 2+-dependent response to the activatory effects of adrenaline, and subsequent inhibition by calcium, suggest capability for a turnover, associated with cyclic changes in membrane potential and participation in a short-term memory pathway. In the cell, the neurotransmitter by activating AC generates intracellular cyclic AMP. Calcium entrance in the cell inhibits the enzyme. The increment of cyclic AMP activates kinase A and their protein phosphorylating activity, allowing a long-term memory pathway. Hence, consolidating neuronal circuits, related to emotional learning and memory affirmation. The activatory effect relates to an enzyme–noradrenaline complex which may participate in the physiology of the fight or flight response, by prolonged exposure. However, the persistence of an unstable enzyme complex turns the enzyme inactive. Effect concordant, with the observation that prolonged exposure to adrenaline, participates in the etiology of stress triggered pathologies. At the cell physiological level AC responsiveness to hormones could be modulated by the concentration of chelating metabolites. These ones produce the release of free ATP 4−, a negative modulator of AC and the Mg 2+ activated insulin receptor tyrosine kinase (IRTK), thus, allowing an integration of the hormonal response of both enzymes by ionic controls. This effect could supersede the metabolic feedback control by energy charge. Accordingly, maximum hormonal response of both enzymes, to high Mg 2+ and low free ATP 4−, allows a correlation with the known effects of low caloric intake increasing average life expectancy.

R(−)2-fluoro-n- n-propylnorapomorphine: A very potent and D 2-selective dopamine agonist

A series of 2-subsdtuted N- n-propylnorapomorphine (NPA) derivatives were synthesized and compared with other DA agonists for affinity to D 1 and D 2 dopamine (DA) receptors in rat brain corpus striatum tissue. The 2-substitutents tested reduced D1 affinity similarly, but enhanced D 2 affinity in the rank order: F > OH > Br > OCH 3 > H ≥ NH 2. The extraordinarily high D 2 affinity (K i = 12 pM) and D 2 vs. D 1 selectivity (57,500) of 2-F-NPA far-exceeded that of all ot DA agonists tested, and it was about 10-times more potent than NPA in vivo.

Chronic bombesin treatment increased the [ 3H]spiperone binding, glutamate decar☐ylase and choline acetyltransferase activity in the rat brain

The effects of chronic bombesin (BBS) on [ 3H]spiperone (SPD) binding activity, choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and glutamate decar☐ylase (GAD) were investigated in the rat brain corpus striatum (CS). The chronic i.p. administration of BBS to rats increased: (1) the specific [ 3H]SPD binding to the striatal P m (plasma membrane) 16%, P < 0.03and34%, P < 0.008 at 5 μg/kg and 10 μg/kg respectively), (2) the specific GAD activity in the CS by 52% (5 μg/kg, n.s.) and 46% (10 μg/kg, P <0.05) respectively, (3) the specific ChAT activity in the CS by 54% (10 μg/kg, P < 0.002) and (4) the specific AChE activity by 23% (10 μg/kg, P < 0.02) after 14 days. It increased only: (1) the specific [ 3H]SPD binding by 29% ( P < 0.001, at 10μg/kg) and (2) the specific GAD activity by 23% ( P < 0.015, 10 μg/kg), after 7 days. Neither ChAT nor AChE activity was affected after 7 days treatment of BBS at 10 μg/kg. In vitro study showed that BBS at 0.2μM did not affect any of the neurochemical parameters examined in the CS. Thus, the changes in brain chemistry caused by chronic BBS were not due to direct effects of BBS but may be mediated through its metabolites or CCK release. Data indicate that the central effects of peripherally administered BBS are dependent on both the duration and the dosage of the drug treatment and that the dopaminergic and GABAergic systems seem to be more vulnerable to chronic BBS than the cholinergic system in the rat brain CS. Results suggest that BBS may play a role in regulating the dopaminergic, GABAergic and cholinergic systems in the brain.

Black widow spider venom-induced release of neurotransmitters: Mammalian synaptosomes are stimulated by a unique venom component (α-Latrotoxin), insect synaptosomes by multiple components

Synaptosomes isolated from the rat brain corpus striatum and locust head and thoracic ganglia were loaded with radioactive neurotransmitter ([ 3H]dopamine and [ 3H]acetylcholine, respectively) and then treated with α-latrotoxin and other fractions (fractions C, D and E of Frontali et al. 8) obtained by Sephadex G200 column chromatography from black widow spider venom gland homogenates. As shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, α-latrotoxin is a high M r protein, whereas fractions C-E are mixtures of several proteins, that include small amounts of contaminating α-latrotoxin (especially in fraction C). In rat synaptosomes α-latrotoxin induced massive neurotransmitter release, and some release was induced also by high concentrations of fractions C and D. These responses were blocked almost completely by a monospecific anti-α-latrotoxin serum, indicating that they were all due to α-latrotoxin. Release of [ 3H]acetylcholine from locust synaptosomes was induced by the various preparations investigated. α-Latrotoxin was about 10-fold less potent in locust than in rat synaptosomes. The effects of fractions C-E tended to disappear with storage. The most active batches of fractions C and E were even more potent than α-latrotoxin, while the D fraction was approximately 5-fold less potent. The anti-α-latrotoxin antiserum inhibited part of the responses elicited by fractions C and E, but left fraction D almost unaffected. Release by D and E fractions was maintained even when Ca 2+ was removed from the incubation medium. It is concluded that locust nerve endings are sensitive not only to α-latrotoxin, but also to other venom components: a high M r toxin (fractions C, D), for which the name of β-latrotoxin is proposed; and, possibly, a third toxin, recovered in the E fraction, that might be immunologically related to α-latrotoxin.

A rat brain isozyme of angiotensin-converting enzyme. Unique specificity for amidated peptide substrates.

We have purified angiotensin-converting enzyme (ACE, EC 3.4.15.1) from rat brain corpus striatum and rat lung. The brain enzyme has Mr 165,000 by sodium dodecyl sulfate gel electrophoresis, whereas the lung enzyme is 175,000. This difference is not an artifact of preparation since mixture of the two tissues prior to purification results in isolation of two proteins with Mr 165,000 and 175,000. Separation of tryptic fragments of 125I-labeled lung and brain ACE by reverse-phase chromatography yields distinct but similar patterns. No differences between the native enzymes are detected in dansyl-tripeptide cleavage specificity, inhibitor profile, immunological properties, sucrose gradient sedimentation, or gel filtration of ACE from the two tissues. However, lung and brain ACE can be differentiated in their ability to cleave amidated peptides. Both lung and brain ACE cleave Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 (substance P) via two pathways. In one pathway, ACE first releases Gly-Leu-Met-NH2 and then dipeptides sequentially from the carboxyl terminus. The other first produces Leu-Met-NH2, and then releases dipeptides to leave substance P 1-5. Lung ACE favors initial tripeptide release 3:1, while the striatal enzyme acts via the two pathways to a similar extent. Lung and striatal ACE also differ in their ability to degrade other amidated peptides. His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 (substance K) and bombesin are degraded by striatal but not lung ACE. Physalaemin and luteinizing hormone-releasing hormone are cleaved by both enzymes, while eledoisin, kassinin, thyrotropin-releasing hormone, and substance P 5-11 are not cleaved by either enzyme. Physalaemin is degraded more rapidly by the lung enzyme. The coincidence of an ACE isozyme with substance P and substance K in the descending striatonigral pathway and the unique ability of this isozyme to cleave substance P and substance K suggest that one or both of these peptides is a physiological substrate for striatonigral ACE.

Activities of glutamine synthetase, glutaminase and arginase in kainic acid lesioned rat brain corpus striatum

Intrastriatal kainic acid (2 μg/μl) administration gave rise to significant increase in activities of glutamine synthetase and arginase along with a significant decrease in the activity of glutaminase in the lesioned striatal tissue 7 days after the administration of kainic acid. The increase in the activity of glutamine synthetase was attributed to the gliosis occurring in such lesions. The decrease in the activity of glutaminase was thought to be due to the loss of GABAergic neurons. The increase in arginase activity might be occurring in glial cells or in nerve endings. Although the earlier results indicated a low specific activity of arginase in glial cells, the observed increase in its activity might be partly due to its increase in proliferating glial cells, liberating ornithine for the formation of polyamines. However, it was also thought that a substantial increase may be occurring in the arginase present in the intact glutamatergic (corticostriate pathway) nerve endings, since it was earlier found that the synaptosomes of the rat brain had appreciably high activity of arginase. These results were discussed in relation to the probable roles of arginine and glutamine as the precursors for neurotransmitter pools of glutamate in striatum.

6,7-Dihydroxy-3-chromanamine: synthesis and pharmacological activity of an oxygen isostere of the dopamine agonist

6,7-Dihydroxy-3-chromanamine, the oxygen isostere of 6,7-dihydroxy-2-aminotetralin (6,7-ADTN), has been synthesized and its dopaminergic activity in various test systems determined. Following bilateral injection into the rat nucleus accumbens, a pattern of locomotor activity similar to that produced by 6,7-ADTN was observed. Its ability to displace N-n-propyl[3H]norapomorphine binding to homogenates of rat brain corpus striatum was found to be about 15 times weaker than 6,7-ADTN and apomorphine. Like 6,7-ADTN it failed to influence dopamine metabolism following an intraperitoneal injection. It is suggested that in addition to the 2-aminotetralins, the 3-chromanamines may be a potential source of new dopamine receptor agonists.

Effect of a stereospecific D2-dopamine agonist on acetylcholine concentration in corpus striatum of rat brain.

The enantiomers of LY141865, trans(+/-)-4,4a,5,6,7,8a,9-octahydro-5-propyl-2H-pyrazolo[3,4-g]qu inoline, were compared as dopamine D2 agonists by determining their abilities to elevate acetylcholine concentrations in rat corpus striatum. The levorotatory isomer, LY156258, increased striatal acetylcholine concentration at doses of 0.1-1 mg/kg i.p., whereas the dextrorotatory isomer had no effect even at doses as high as 30 mg/kg. The levorotatory isomer also decreased striatal concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, but did not significantly alter dopamine or 5-hydroxyindoleacetic acid concentration. The dextrorotatory isomer had no effect on any of these substances alone and did not alter the effects of the levorotatory isomer. The elevation of striatal acetylcholine levels by LY156258 was mimicked by pergolide, a dopamine agonist, and was totally prevented by pretreatment with haloperidol, a dopamine antagonist. The elevation of striatal acetylcholine concentration by LY157258 was maximal at 0.5 hour and declined thereafter, following a time course similar to that of pergolide. Neither LY141865 nor LY156258 shared with peroglide and dopamine the ability to activate striatal adenylate cyclase in vitro, an effect mediated by D1 receptors. LY141865 and LY156258 (but not the dextrorotatory isomer) inhibited the binding of tritiated apomorphine and spiperone to striatal membrane receptors, but were not as potent as pergolide, they also had less effect, or no effect, on the binding of other tritiated ligands (dopamine, WB4101, clonidine, dihydroalprenolol, pyrilamine or quinuclidinyl benzilate) to their membrane receptors. These results indicate that LY156258 stereospecifically activates dopamine D2 receptors and the studies are the first evidence of sterospecificity of dopamine receptors mediating an increase in striatal acetylcholine concentration.

Competitive inhibition of catecholamine uptake in synaptosomes of rat brain by rigid bicyclo-octanes.

Abstract: Cis‐3‐(3, 4‐dichlorophenyl)‐2‐N, N‐dirnethylaminomethyl‐bi‐cyclo‐[2, 2, 2]‐octane hydrochloride (LR5182) inhibited the uptake of dopamine by a synaptosomal fraction of corpus striatum of rat brain with an inhibitor constant (Ki value) of 6 nM. Kinetics analysis according to the methods of Lineweaver‐Burk and Dixon revealed a competitive inhibition of dopamine uptake of LR5182. When the uptake of dopamine by the noradrenergic terminals in the synaptosomal fraction of cerebral cortex was selectively abolished by desipramine, LR5182 competitively inhibited the uptake of dopamine by the dopaminergic terminals with a Ki value of 19 nM. LR5182 was also a competitive inhibitor of noradrenaline uptake by synaptosomes of hypothalamus and cerebral cortex with, however, one‐third to one‐tenth the effectiveness, as indicated by the larger Ki values, 52 and 58 nM, respectively. Structure‐activity studies with LR5182 and related compounds supported the idea that the uptake sites of dopamine favored a gauche conformer.

Effects of chronic lithium administration on concanavalin A binding to plasma membranes from the corpus striatum of rat brain

The effects of chronic in vivo lithium administration on mannose-containing components of plasma membranes from rat corpus striatum were examined by a 3H-concanavalin A binding displacement method. No difference on Con A binding was observed between sodium or lithium-treated rats during a 1-month period.

Effects of plant lectins on cation-activated brain ATPases

Abstract The effects of concanavalin A (con A) and wheat germ agglutinin (WGA) on cation-activated ATPases in a crude homogenate of rat brain corpus striatum were examined. Con A enhanced the activity of Mg++-dependent-, and Ca++-activated-ATPases, and inhibited (Na+ + K+)- ATPase activity. WGA enhanced Mg++-dependent ATPase activity, but did not alter the activity of the other two components. The specificity of these interactions was demonstrated by reversal with specific lectin-interacting sugars. The possibility that these effects may be mediated by lectin-binding to physiologic regulatory sites, as well as the possible role of these interactions in the etiopathology of schizophrenia are discussed.

The effects of repeated D-lysergic acid diethylamide injections on catecholamine levels and tyrosine hydroxylase activity in rat brain regions.

Abstract—Daily injections of 100 μg/kg of d‐lysergic acid diethylamide (LSD) for 14 days produced a significant decrease in the dopamine level in rat brain corpus striatum which was still apparent 15 days after the last LSD treatment. Further LSD injections did not change the amount of dopamine depletion. In cerebral cortex, 14 days of LSD injections produced a significant decrease in the norepinephrine level and a significant increase in tyrosine hydroxylase activity. The elevated tyrosine hydroxylase activity was still present 15 days after the final LSD injection but only in those animals receiving daily vehicle injections during this period. Pre‐treatment of rats with daily saline injections for 2 weeks before the 2 week period of LSD treatment prevented both the reduced norepinephrine content and elevated tyrosine hydroxylase activity usually found 24 h after the last LSD injection.

Comparison of effects of drugs on dopamine metabolism in the substantia nigra and the corpus striatum of rat brain

The influence of apomorphine, chloral hydrate, haloperidol, morphine, oxitremorine, pargyline, probenecid and promethazine on DOPAC and HVA levels was studied in the substantia nigra (including the ventral tegmental dopaminergic regions) and corpus striatum of the rat brain. The time-effect curves of changes in HVA levels after pretreatment with apomorphine, haloperidol, morphine, oxotremorine or promethazine are presented. The time-effect curves for the substantia nigr showed an initial rapid HVA rise, which was not observed in the corpus striatum. Promethazine treatment caused a small but significant HVA rise in the substantia nigra only. Chloral hydrate, morphine and oxotremorine induced a similar percentage increase in DOPAC and HVA levels in the substantia nigra as well as in the corpus striatum. Haloperidol, however, caused a small percentage change in the metabolite levels in the substantia nigra when compared to the pronounced rise seen in the corpus striatum. The apomorphine-induced HVA decrease observed in both structures provides evidence for the presence of a dopaminegic receptor in the substantia nigra.

Dopamine-sensitive adenylate cyclase and cAMP phosphodiesterase in substantia nigra and corpus striatum of rat brain

A dopamine-sensitive adenylate cyclase has been identified in substantia nigra of the rat brain. Low concentrations of dopamine markedly increased the accumulation of cyclic AMP while l-norepinephrine and isoproterenol had little effect at concentrations up to 100 μM. The phenothiazine, trifluoperazine, is a potent inhibitor of the s. nigral adenylate cyclase (I.C. 50 of 0.1 μM), while the adrenergic receptor blocking agents propranolol and phentolamine are ineffective. Basal activity of striatal adenylate cyclase and cAMP phosphodiesterase is approximately 3-fold higher than that found in substantia nigra.

Antipsychotic drugs and dopamine-stimulated adenylate cyclase prepared from corpus striatum of rat brain.

Antipsychotic drugs and their clinically impotent congeners were examined as inhibitors of dopamine-sensitive adenylate cyclase (EC 4.6.1.1) in cell-free membrane preparations of the caudate-putamen of rat brain. Of 12 neuroleptic drugs with reported antipsychotic efficacy, all inhibit stimulation of adenylate cyclase by 40 muM dopamine at micromolar concentrations. Among 14 other structurally related drugs that are not clinically effective as antipsychotic agents, 12 were almost ineffective while two drugs were moderate inhibitors of dopamine-sensitive adenylate cyclase.

Nomifensine: a new potent inhibitor of dopamine uptake into synaptosomes from rat brain corpus striatum.

Nomifensine: a new potent inhibitor of dopamine uptake into synaptosomes from rat brain corpus striatum.

Effect of Psychoactive Drugs on Dopamme(3,4-Dihydroxyphenethylamine)-Sensitive Adenylate Cyclase Activity in Corpus Striatum of Rat Brain

Effect of Psychoactive Drugs on Dopamme(3,4-Dihydroxyphenethylamine)-Sensitive Adenylate Cyclase Activity in Corpus Striatum of Rat Brain

The influence of oxotremorine on iron and flavines in mitochondria from rat brain corpus striatum

The influence of oxotremorine on iron and flavines in mitochondria from rat brain corpus striatum