The effect of X-irradiation on the amount of dopamine in corpus striatum of the rat

Summary The effect of ionizing radiation on the amount of dopamine in corpus striatum was investigated in rats exposed to 650 or 850 R of X-rays. The amount of dopamine in the corpus striatum was measured fluorimetrically in various periods of time after irradiation. It was found that, irrespective of the dose applied, the ionizing radiation caused a significant depletion of dopamine in the striatum.     

Effect of benzatropine on the O-methylation of striatal dopamine]

After treatment by nialamid, benztropine administered to Rats produced an increase in the level of 3-O-methyldopamine in the corpus striatum. It produced a slight increase in the level of striatal dopamine and no change in the level of norepinephrine. The monoamine oxydase and catechol-O-methyltransferase activities of remaining brain showed no variations by benztropine. The results suggest the possible involvement of striatal dopamine and its extraneuronally catabolism in the antiparkinsonian effect of benztropine.     

Effects of penfluridol of dopamine-sensitive adenylate cyclase in corpus striatum and substantia nigra of rats.

Penfluridol, a neuroleptic with diphenylbutyl piperidine structure, blocked the dopamine-sensitive adenylate cyclase in homogenates of corpus striatum and substantia nigra of rats, probably by a competitive antagonism versus dopamine.     

Serotoninergic modulation of mesolimbic and frontal cortical dopamine neurons

Summary Potentiation of the effect of haloperidol on dopamine metabolism by the 5-HT uptake inhibitor CGP 6085 A, and antagonism of this effect by the 5-HT antagonist mianserin were observed in the mesolimbic area and the frontal cortex of the rat brain. A similar effect was reported earlier in the corpus striatum. This suggests that serotoninergic modulation of dopamine neurons is a generally-occurring phenomenon in the brain.     

Serotoninergic modulation of mesolimbic and frontal cortical dopamine neurons

Potentiation of the effect of haloperidol on dopamine metabolism by the 5-HT uptake inhibitor CGP 6085 A, and antagonism of this effect by the 5-HT antagonist mianserin were observed in the mesolimbic area and the frontal cortex of the rat brain. A similar effect was reported earlier in the corpus striatum. This suggests that serotoninergic modulation of dopamine neurons is a generally-occurring phenomenon in the brain.     

Effects of levophacetoperane, pemoline, fenozolone, and centrophenoxine on catecholamines and serotonin uptake in various parts of the rat brain]

These drugs, except centrophenoxine, inhibit in vitro in a competitive manner, norepinephrin uptake in Rat hypothalamus and cortex, and dopamine uptake in corpus striatum and cortex, at higher concentrations than d.l. amphetamine; this alone inhibits serotonin uptake in hypothalamus.     

Effects of penfluridol on dopamine-sensitive adenylate cyclase in corpus striatum and substantia nigra of rats

Summary Penfluridol, a neuroleptic with diphenylbutyl piperidine structure, blocked the dopamine-sensitive adenylate cyclase in homogenates of corpus striatum and substantia nigra of rats, probably by a competitive antagonism versus dopamine.Acknowledgment. We thank Dr P. Janssen (Beerse, Belgium) for a generous gift of penfluridol.     

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.     

L-threo-3,4-dihydroxyphenylserine,a noradrenaline precursor,inhibits dopamine release and metabolism in the rat striatum in vivo

The effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on dopamine (DA) release and metabolism in the striatum was studied in freely moving rats by intracerebral microdialysis techniques. The DA level as well as the levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly decreased 140 min after the administration of L-threo-DOPS (50 mg/kg intraperitoneally). The results suggest that L-threo-DOPS inhibits the release and metabolism of DA in the striatum.     

L-threo-3,4-dihydroxyphenylserine, a noradrenaline precursor, inhibits dopamine release and metabolism in the rat striatum in vivo.

The effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on dopamine (DA) release and metabolism in the striatum was studied in freely moving rats by intracerebral microdialysis techniques. The DA level as well as the levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly decreased 140 min after the administration of L-threo-DOPS (50 mg/kg intraperitoneally). The results suggest that L-threo-DOPS inhibits the release and metabolism of DA in the striatum.     

Accumulation of 3H-dopamine by synaptic vesicles from rat striatum in an impermeant medium

The accumulation of 3H-dopamine by synaptic vesicles from rat striatum was significantly stabilized in a membrane impermeant medium. The characteristics of dopamine accumulation by striatal vesicles were quite similar to those reported for dopamine accumulation by a whole brain vesicle preparation in the same medium, and were significantly different from the characteristics previously reported for vesicular accumulation of norepinephrine.     

Regulation of the cell cycle following DNA damage in normal and Ataxia telangiectasia cells

A proportion of the population is exposed to acute doses of ionizing radiation through medical treatment or occupational accidents, with little knowledge of the immedate effects. At the cellular level, ionizing radiation leads to the activation of a genetic program which enables the cell to increase its chances of survival and to minimize detrimental manifestations of radiation damage. Cytotoxic stress due to ionizing radiation causes genetic instability, alterations in the cell cycle, apoptosis, or necrosis. Alterations in the G1, S and G2 phases of the cell cycle coincide with improved survival and genome stability. The main cellular factors which are activated by DNA damage and interfere with the cell cycle controls are: p53, delaying the transition through the G1-S boundary; p21^WAF1/CIPI, preventing the entrance into S-phase; proliferating cell nuclear antigen (PCNA) and replication protein A (RPA), blocking DNA replication; and the p53 variant protein p53as together with the retinoblastoma protein (Rb), with less defined functions during the G2 phase of the cell cycle. By comparing a variety of radioresistant cell lines derived from radiosensitive ataxia talangiectasia cells with the parental cells, some essential mechanisms that allow cells to gain radioresistance have been identified. The results so far emphasise the importance of an adequate delay in the transition from G2 to M and the inhibition of DNA replication in the regulation of the cell cycle after exposure to ionizing radiation.     

A preliminary study on the behaviour and biochemical responses subsequent to the injection of 5,6-dihydroxytryptamine into the substantia nigra of the rat.

Injection of 5,7-dihydroxytryptamine into the substantia nigra of rats produces an increase of dopamine in the ipsilateral striatum, and when these animals are injected with amphetamine they do not exhibit any rotation. The mode of action of this neurotoxin is compared with that of 6-hydroxydopamine.     

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

Summary The effects of chronic in vivo lithium administration on mannose-containing components of plasma membranes from rat corpus striatum were examined by a³H-concanavalin A binding displacement method. No difference in Con A binding was observed between sodium or lithium-treated rats during a 1-month period.We thank Dr S. Gershon of this research unit for his encouragement and support during these studies.     

A preliminary study on the behaviour and biochemical responses subsequent to the injection of 5,6-dihydroxy-tryptamine into the substantia nigra of the rat

Summary Injection of 5,7-dihydroxytryptamine into the substantia nigra of rats produces an increase of dopamine in the ipsilateral striatum, and when these animals are injected with amphetamine they do not exhibit any rotation. The mode of action of this neurotoxin is compared with that of 6-hydroxydopamine.     

Massive striatal dopamine release in acute cerebral ischemia in rats

Summary Extracellular dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and cerebral blood flow were simultaneously determined using in vivo brain dialysis and a hydrogen clearance method in the striatum of spontaneously hypertensive rats during ischemia and after recirculation. Massive striatal dopamine release was demonstrated in acutely induced ischemic brain.     

Increase in in vivo (3H) spiperone binding in the rat hippocampal formation and striatum after repeated treatment with haloperidol

Summary An increase in in vivo (³H) spiperone binding was observed in rat hippocampal formation and striatum after repeated treatment with haloperidol. This suggests that in hippocampus as well as in striatum prolonged blockade of dopaminergic transmission by a neuroleptic agent results in the development of a supersensitivity of the dopamine receptors.Acknowledgments. We wish to thank Mrs J. Krauss for skillful technical assistance, Drs Helmut Bittiger and Rainer Ortmann for helpful discussions.     

Accumulation of3H-dopamine by synaptic vesicles from rat striatum in an impermeant medium

Summary The accumulation of³H-dopamine by synaptic vesicles from rat striatum was significantly stabilized in a membrane impermeant medium. The characteristics of dopamine accumulation by striatal vesicles were quite similar to those reported for dopamine accumulation by a whole brain vesicle preparation in the same medium, and were siginificantly different from the characteristics previously reported for vesicular accumulation of norepinephrine.Acknowledgments. This work was supported by grant NS 18752 (NIH) of the United States Public Health Service. Reprint requests to J. A. R.     

Effect of acetylcholine acetyl-hydrolase (E.C. 3.1.1.7) inhibition on the accumulation of pp' DDT in various brain regions of rats

Summary The concentration of pp' DDT given intraperitoneally in rats was determined in different brain regions. Maximum accumulation of pp' DDT was found in the corpus striatum, followed by cerebellum and cerebral cortex in that order; following pretreatment with paraoxon the concentrations of pp' DDT were increased in all brain regions studied. pp' DDT (1,1,1-trichloro-2,2-bis(4′-chlorophenyl ethane), used in the above studies was generously supplied by Montrose Chemical Corporation of California, USA. The authors are grateful to Mr M.Z. Hasan for analysis of the samples and to Sandoz, Basel, Switzerland for the gift of paraoxon.     

Monoamine oxidase inhibitors antagonize the acceleration of brain dopamine synthesis induced by neuroleptic drugs in vivo: Implications for the treatment of tardive dyskinesia

Zusammenfassung Pargylin und Pheniprazin vermindern stark die Dopa-Anreicherung (erhöhte Dopamin-Synthesegeschwindigkeit) im corpus striatum der Ratte nach Trifluoperazin und Tetrabenazin. Dopamin-spezifische MAO-Hemmer könnten deshalb therapeutischen Wert haben in der Kontrolle von tardiver Dyskinesia, die möglicherweise durch erhöhte Bildung und Umsatz von Dopamin unter dem Einfluss von anti-psychotischen Drogen hervorgerufen wird.