PubMed Health⌕ Search

Biomedical subjects

B Scatton

Publications and source records attributed to B Scatton.

At least 199 records · Page 11Linked to original sources
PubMed1984

Increase in dopamine and DOPAC levels in noradrenergic terminals after electrical stimulation of the ascending noradrenergic pathways.

The effect of electrical stimulation of the ascending noradrenergic neurons on the formation of dopamine and its major deaminated metabolite dihydroxyphenylacetic acid (DOPAC) in the hippocampal formation, a predominantly noradrenaline-rich brain area, has been investigated in the rat. Electrical stimulation of the locus coeruleus or ascending noradrenergic pathways caused a pronounced increase in hippocampal dopamine and DOPAC levels which paralleled the increase in free and conjugated dihydroxyphenylethyleneglycol levels. The elevation of hippocampal DOPAC was no longer seen after chemical lesion of the noradrenergic pathways. It is suggested that the enhanced formation of dopamine and DOPAC in hopocampal noradrenergic terminals under conditions of increased noradrenergic impulse flow may be connected to an inefficient beta-hydroxylation of dopamine to noradrenaline with a subsequent oxidative deamination of dopamine into its degradation products.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

[3H]spiperone binding, dopamine and HVA concentrations in Parkinson's disease and supranuclear palsy.

The density of D2-type dopamine receptors, measured by the binding of [3H]spiperone was normal in the substantia nigra, caudate nucleus and nucleus accumbens of Parkinsonian subjects and above control levels in the putamen, in spite of massive lesions of the dopaminergic neurons. Dopamine levels were reduced in the putamen, caudate nucleus, and nucleus accumbens by 97, 85 and 68%, respectively and by 78 and 93% in the pars compacta and pars reticulata of the substantia nigra. HVA levels were much less affected suggesting that increased activity of the remaining dopaminergic neurons compensated to some extent for the lesions. Neuroleptic treatment and the presence of dementia in the Parkinsonian subjects affected [3H]spiperone binding and dopamine concentrations. Dopamine and HVA levels in the striatum of subjects with supranuclear palsy indicate that the nigrostriatal system was lesioned to the same degree in this disease as in idiopathic Parkinsonism, but spiperone binding was reduced by half in all the structures studies.

Aged↗
PubMed1984

Decrease in both choline acetyltransferase activity and EEG patterns in the hippocampal formation of the rat following septal macroelectrode implantation.

A decrease in both choline acetyltransferase (CAT) activity and theta (theta) rhythm were observed in the hippocampal formation of rats implanted with a macroelectrode in the dorsomedial part of the septum. The decrease in CAT activity and in theta occurred simultaneously and in parallel, and there was no instance where the two parameters were uncoupled. These observations suggest that a common neurophysiological mechanism is involved in both CAT activity control and theta rhythm production in the hippocampal formation. From a methodological point of view, these observations should be borne in mind in septohippocampal investigations using septal electrode implantation procedures.

Animals↗
PubMed1984

Hypophysectomy fails to affect the supersensitivity of striatal dopamine target cells induced by prolonged haloperidol treatment.

The influence of hypophysectomy on biochemical indices of striatal dopamine target cell supersensitivity induced by prolonged haloperidol treatment was investigated in the rat. Hypophysectomy itself did not modify dihydroxyphenylacetic acid (DOPAC) levels but slightly enhanced acetylcholine concentrations in the striatum. Hypophysectomy failed to affect the ability of haloperidol, apomorphine and pergolide to alter these biochemical parameters after acute administration. Prolonged administration of haloperidol (by means of osmotic minipumps delivering 2.5 micrograms/h) for 14 days caused a decrease in DOPAC and an increase in acetylcholine levels in the striatum during withdrawal; these effects were of a similar magnitude in sham-operated and hypophysectomized rats. Moreover, there was a similar degree of tolerance to the elevation of DOPAC and to the diminution of acetylcholine concentrations in striatum in response to challenge with haloperidol during withdrawal in sham-operated and hypophysectomized animals. Finally, a similar supersensitive biochemical response to pergolide (decrease in DOPAC and increase in acetylcholine levels) was observed in both hypophysectomized and sham-operated animals after prolonged haloperidol treatment. These data suggest that hypophyseal factors do not affect the development of striatal dopamine target cell supersensitivity caused by prolonged haloperidol treatment.

Acetylcholine↗
PubMed1984

Effects of cyclo (Leu-Gly) on neurochemical indices of striatal dopaminergic supersensitivity induced by prolonged haloperidol treatment.

The effects of a prolonged treatment with cyclo (Leu-Gly) and/or haloperidol on biochemical parameters indicative of striatal dopamine target cell supersensitivity have been investigated in the rat. When given acutely, cyclo (Leu-Gly) (2 mg/kg sc) did not affect striatal homovanillic acid, dihydroxyphenylacetic acid and acetylcholine levels both under basal conditions or after acute haloperidol (1 mg/kg ip) treatment. When given concomitantly with haloperidol (infused by means of osmotic minipumps at a rate of 2.5 micrograms/h sc) for 14 days, cyclo (Leu-Gly)(2 mg/kg sc once daily) failed to prevent the fall of striatal dopamine metabolites observed 2 days following withdrawal and the tolerance to the elevation of dopamine metabolites which occurs in response to challenge with the neuroleptic during withdrawal. Prolonged treatment with cyclo (Leu-Gly) also failed to affect the tolerance to the decrease of striatal acetylcholine levels which occurs under chronic haloperidol treatment. These data suggest that the mechanism whereby cyclo (Leu-Gly) inhibits the development of neuroleptic-induced dopaminergic supersensitivity does not involve an action of the peptide on nigro-striatal dopaminergic and striatal cholinergic neurons and is probably exerted distally to both dopaminergic and cholinergic synapses.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Autoradiographic localization of dopamine receptors in the spinal cord of the rat using [3H]-N-propylnorapomorphine.

Dopamine receptors were localized autoradiographically in the rat spinal cord after in vitro labelling using 3H-N-propylnorapomorphine (NPA). The highest densities of 3H-NPA binding sites were found in the substantia gelatinosa and in a zone of the grey matter immediately ventral to the dorsal corticospinal tract. Other areas of the grey matter presented only moderate or low receptor densities while no 3H-NPA binding sites could be found in the white matter. The localization of 3H-NPA binding sites is compatible with a role for spinal cord dopamine in the processing of sensory information.

Animals↗
PubMed1984

Indoleaminergic mechanisms in brain vessels; localization, concentration, uptake and in vitro responses of 5-hydroxytryptamine.

Immunocytochemical studies have revealed the presence of 5-HT-containing nerve fibres in all parts of the cerebrovascular bed (arteries, arterioles and veins) of mouse, rat, guinea-pig, rabbit and cat. Biochemical measurements (using HPLC) revealed substantial concentrations of 5-HT and 5-HIAA in the pial vessels of the rat, rabbit, cat and man, the amounts corresponding well with the density of the perivascular nerve supply. The uptake of 3H-5-HT was studied in arteries removed from the circle of Willis in rats. Maximum uptake was reached after 15 min of incubation at 37 degrees C and plateaued at 30 min. The reaction was temperature-dependent and found to be absent if performed at 0 degrees C. Pharmacological experiments on isolated middle cerebral and basilar arteries showed that vessels from rat and dog were contracted by approximately 90% upon administration of 5-HT, whereas vessels from guinea-pig, rabbit, cat and man were contracted by 40 to 60% relative to 124 mM K+. The EC50 values in the different species varied by between 1.5 X 10(-7) M (rat) and 3 X 10(-9) M (dog). The 5-HT-induced contractions were blocked by the 5-HT antagonists, methysergide, methergoline and ketanserin. Transmural nerve stimulation (TNS) of the rabbit basilar artery revealed a tetrodotoxin sensitive constriction whereas TNS of cat and dog middle cerebral arteries caused a tetrodotoxin-sensitive relaxation. The relaxation was not significantly attenuated until high doses of methergoline (3 X 10(-6) M) or ketanserin (3 X 10(-5) M) had been given.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Evidence for a GABAergic inhibitory influence on serotonergic neurons originating from the dorsal raphe.

Systemic administration of progabide, dipropylacetamide and gamma-acetylenic-GABA diminished striatal 5-HTP accumulation; the effect of progabide was abolished after hemitransection. Intradorsal raphé (but not intrastriatal) infusion of GABA or GABA agonist agents reduced striatal 5-HTP accumulation. Infusion of picrotoxinin or bicuculline into the dorsal raphé was without effect. It is concluded that GABA exerts an inhibitory influence on striatal serotonergic transmission via stimulation of GABA receptors located in the dorsal raphé.

5-Hydroxytryptophan↗
PubMed1983

[3H]imipramine binding in subcellular fractions of rat cerebral cortex after chemical lesion of serotonergic neurons.

The specific high affinity binding of [3H]imipramine was investigated in subcellular fractions of rat cerebral cortex before and after chemical denervation of serotonergic neurons. In control animals the proportion of the total number of [3H]imipramine binding sites in the nuclear (N), heavy mitochondrial (M), light mitochondrial (L) and microsomal (P) fractions corresponded respectively to 3, 45, 16 and 36% of the total number of binding sites. After chemical lesion of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) the density of [3H]imipramine binding sites in fractions M and L was decreased by 42 and 52% respectively. In these experiments the uptake of [3H]5-HT in fractions M and L decreased by approximately 80%. The Bmax of [3H]imipramine binding in fraction P was decreased by 80% after chemical denervation with 5,7-DHT. In the control group there was no detectable [3H]5-HT uptake while the endogenous serotonin levels in fraction P were rather low. Our results support the view that the high affinity binding of [3H]imipramine is partly located on serotonergic nerve terminals. The significance of the [3H]imipramine binding sites present in the microsomal (P) fraction remains to be clarified.

5,7-Dihydroxytryptamine↗
PubMed1983

[3H]RX 781094: a new antagonist ligand labels alpha 2-adrenoceptors in the rat brain cortex.

[3H]RX 781094 [(imidazolinyl-2)-2 benzodioxane-1,4 [3H]chlorhydrate], a specific alpha 2-adrenoceptor antagonist radioligand, has been used to characterize alpha 2-adrenoceptors in rat cortical membranes. [3H]RX 781094 binding is reversible, saturable and stereospecific. It labels with high affinity a single population of non-interacting sites. The KD value was 3.9 +/- 0.4 nM and the Bmax 189.0 +/- 12.4 fmol/mg protein. Competition curves with different alpha-adrenoceptor agonists and antagonists showed that the binding sites labelled with [3H]RX 781094 had the pharmacological characteristics of alpha 2-adrenoceptors. Pretreatment with reserpine (2.5 mg/kg s.c., 24 h before the experiment) did not affect the KD or Bmax values of [3H]RX 781094 binding. Chemical destruction of noradrenergic pathways by systemic injection of DSP4 or intracerebral injection of 6-hydroxydopamine did not modify the KD or the Bmax of [3H]RX 781094 binding. It is concluded that the major proportion of alpha 2-adrenoceptors labelled with [3H]RX 781094 are not localised to noradrenergic nerve terminals.

Adrenergic alpha-Antagonists↗
PubMed1983

Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease.

Dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, noradrenaline, serotonin and 5-hydroxyindoleacetic acid concentrations were measured in several cortical areas, hippocampus and, for comparison, in the caudate nucleus, from control subjects and parkinsonian patients. Substantial amounts of these compounds were detected in hippocampus, and entorhinal, cingulate and frontal cerebral cortices of control subjects. In patients who had discontinued L-DOPA at least 4 days before death (group I), the levels of dopamine and its metabolites were reduced in these cortical areas, although to a lesser extent than in the caudate nucleus. In patients on continuous L-DOPA treatment (i.e. having received the last dose of L-DOPA 0-24 h before death, group II), cortical dopamine levels were less reduced than in group I patients and dopamine metabolite levels were similar to those of controls. The ratio of the concentrations of homovanillic acid to dopamine was increased in the caudate nucleus and entorhinal cortex but not in the other cortical areas of group I parkinsonian patients. Cortical noradrenaline concentrations were also diminished, the decrement being similar in groups I and II. A reduction of serotonin and its metabolite in the caudate nucleus and hippocampus and a diminution of serotonin levels in the frontal cortex were observed in group I patients. In these patients, the 5-hydroxyindoleacetic acid to serotonin ratio was increased in the caudate nucleus and frontal cortex but not in the other cortical areas. The results are discussed in relation to the pathophysiology of the psychiatric and cognitive disturbances observed in some parkinsonian patients.

Aged↗
PubMed1983

Influence of lithium on biochemical manifestations of striatal dopamine target cell supersensitivity induced by prolonged haloperidol treatment.

The effects of prolonged treatment with dietary lithium and/or haloperidol (infused by means of osmotic minipumps) on biochemical parameters indicative of striatal dopamine target cell supersensitivity have been investigated in the rat. When given concomitantly with haloperidol, lithium failed to prevent the fall of striatal dopamine metabolites observed 2 days following withdrawal and the tolerance to the elevation of dopamine metabolites in response to challenge with the neuroleptic during withdrawal. Prolonged treatment with lithium also failed to modify the changes in nigral dihydroxyphenylacetic acid levels and in striatal acetylcholine levels which occur under chronic neuroleptic treatment. Chronic dietary lithium alone consistently elevated substance P levels in substantia nigra. The usual decrease in nigral levels of the peptide that occurs in response to chronic treatment with haloperidol was prevented in animals treated concomitantly with lithium. These data suggest that the mechanism whereby lithium stabilizes dopaminergic supersensitivity does not seem to involve an action of the compound on the neuronal mechanisms regulating the activity of the nigro-striatal dopaminergic system or on striatal cholinergic neurons but may be related to the restoration of normal striato-nigral substance P ergic transmission.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Alterations of noradrenaline and serotonin uptake and metabolism in chronic cobalt-induced epilepsy in the rat.

The high affinity uptake of noradrenaline and serotonin, and the concentrations of these monoamines and their metabolites, have been measured in the perifocal cortical area at various stages of the evolution of cobalt-induced epilepsy in the rat. Noradrenaline uptake was maximally reduced at days 8-10 after cortical cobalt application, a time corresponding to the onset of epileptic discharges; it remained diminished during the spiking activity period of the focus (days 14-20) and was back to normal values at day 40, at which time the epileptic syndrome had disappeared. Serotonin uptake was also diminished at days 8-10 but to a lesser extent than was noradrenaline uptake. In the homotopic cerebral cortex contralateral to cobalt application, noradrenaline uptake was reduced at day 10 only and to a lesser extent than in the perifocal area, whereas serotonin uptake was unaffected. Kinetic analysis of the cobalt-induced monoamine uptake alterations at day 10 revealed a diminution of the maximal velocity with no change in the Km. Noradrenaline and dihydroxyphenylethyleneglycol concentrations in the perifocal area were also maximally reduced at days 8-10 but were unaffected at day 2 and day 40 post cobalt application. A reduction of serotonin levels in the perifocal area was observed only at days 8-10 while 5-hydroxyindoleacetic acid remained unaffected throughout the time period studied. The levels of these monoamines and their metabolites were unchanged in the homotopic contralateral cortex 2-40 days after cobalt application. These results indicate that cortical cobalt application induces alterations of the biochemical indices of the density of noradrenaline-containing terminals that closely parallel the evolution of the epileptic syndrome. These data further emphasize the important role of the cortical noradrenergic system in cobalt-induced epilepsy.

Animals↗
PubMed1983

The potential use of GABA agonists in psychiatric disorders: evidence from studies with progabide in animal models and clinical trials.

Progabide, a new antiepileptic GABA agonist of moderate affinity for GABA receptors, has been studied in a number of psychiatric disorders and the results compared with the action of this drug in animal models. In an animal model for anxiety (the aversive response to periaqueductal grey stimulation in the rat) progabide had a similar action to that of diazepam. However in clinical trials to date the effect of the GABA agonist was inferior to that of benzodiazepines. As progabide diminishes both the nigrostriatal dopamine neuron activity and the effects of striatal dopamine receptor activation, a trial in schizophrenic patients was undertaken. Progabide was devoid of any evident antipsychotic action. However a certain improvement in responsiveness to the environment and in social interactions was noticed in hebephrenic and schizoaffective syndromes. This lack of antipsychotic effect of progabide may be a reflection of the weak activity of GABA agonists on limbic dopamine neurons. In these various clinical trials a definite improvement of affect and mood was noted in those patients receiving progabide. In clinical trials in depressed patients progabide produces a significant reduction in depressive symptoms, an action similar to that of imipramine both for the global clinical rating and the HRSD. This antidepressant activity is reflected by the action of progabide in behavioural models of depression such as olfactory bulbectomy, learned helplessness and the sleep-wake cycle.

Adjustment Disorders↗
PubMed1983

Pharmacological and therapeutic actions of GABA receptor agonists.

GABA receptor agonists, e.g. progabide, modify the activity of several brain neuronal systems which are implicated in the pathogenesis of some neuropsychiatric disorders. Thus, alterations in noradrenergic and serotoninergic transmissions induced by progabide may be a mechanism involved in the antidepressant action of this drug in the clinic. The antagonism of the neuroleptic-induced increase in dopamine receptor sensitivity and the decrease in dopamine synthesis and release may be responsible for the effectiveness of the GABA receptor agonists in the treatment of neuroleptic- and L-DOPA-induced dyskinesia. This action of GABA receptor agonists also suggests their therapeutic potential in mania. Finally, decrease in cellular excitability induced by GABA receptor agonists, e.g. progabide, accounts for their efficacy in epilepsy.

Bipolar Disorder↗