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Biomedical subjects

B Scatton

Publications and source records attributed to B Scatton.

249 records · Page 14Linked to original sources
PubMed1978

Subsensitivity of striatal and mesolimbic dopamine target cells after repeated treatment with apomorphine dipivaloyl ester.

The effects of acute and repeated treatments with the dipivaloyl ester of apomorphine on behaviour and brain dopamine metabolism were compared in rats. A single injection of the ester (50 mg/kg i.p.) indued a stereotyped behaviour lasting for at least 6 h and a concomitant decrease in striatal HVA levels. After repeated treatment (twice daily for 7 days) with the drug, both the stereotyped behaviour and the decreases in striatal HVA levels were attenuated as compared to acute treatment; the minimal dose tested which induced this tolerance was found to be 25 mg/kg i.p. The minimal length of treatment with 50 mg/kg of the ester after which tolerance was observed was 3-4 days. The ED50 for haloperidol-induced catalepsy was about 4 times lower in rats treated with apomorphine dipivaloyl ester (50 mg/kg) for 7 days than in naive rats. Similarly, a shift to the left of the haloperidol dose-response curve for the increase in striatal dopamine metabolite levels was observed in rats treated subacutely with the ester as compared to control rats. Repeated treatment (7 days) with the dipivaloyl ester of apomorphine also attenuated the decrease in NVA levels seen with acute treatment in nucleus accumbens and tuberculum olfactorium; however, the threshold dose inducing tolerance in limbic regions was higher than in striatum. No difference in the brain concentrations of apomorphine was found after acute and repeated treatments with the ester. Thus, the present study provides evidence for the development of subsensitivity of dopamine receptors after repeated administration of aopomorphine dipivaloyl ester.

Animals↗
PubMed1977

Differential regional development of tolerance to increase in dopamine turnover upon repeated neuroleptic administration.

Repeated treatment with haloperidol and sulpiride induced tolerance to the increases in homovanillic and dihydroxyphenyl acetic acids in the striatum, nucleus accumbens, tuberculum olfactorium and frontal cortex of the rat. The threshold dose inducing this effect appeared to be lower in the striatum than in the limbic regions. Similar results were found in the frontal cortex by measuring dopamine utilization. Moreover, tolerance developed earlier in the striatum than in the limbic areas. The possible reasons are discussed for the differential development of tolerance in the various DA areas investigated.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1977

Regional effects of neuroleptics on dopamine metabolism and dopamine-sensitive adenylate cyclase activity.

The effect of haloperidol, chlorpromazine, thioridazine and sulpride on the levels of DOPAC and HVA, as an index of DA turnover, and on the activity of DA-stimulated adenylate cyclase was investigated inthe striatum, the nucleus accumbens and the tuberculum olfactorium of the rat brain. Haloperidol, chlorpromazine and thioridazine caused a more marked increase in DA turnover in the striatum than in the mesolimbic areas, while the reverse was true for sulpiride. In contrast, although the relative potency of these compounds varied greatly, the Ki of each drug for the DA-sensitive adenylate cyclase was similar in three structures of rat brain. The results indicate that in the three brain structures investigated there was no correlation between the differential effects of neuroleptics on dopamine turnover in vivo and the blockade by these drug of the DA-sensitive adenylate cyclase activity in vitro.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1975

Acute and subacute effects of neuroleptics dopamine synthesis and release in the rat striatum.

The effects of acute and subacute treatments with moderate doses of thioproperazine and haloperidol on dopamine synthesis and release have been examined in rat striatal slices. Synthesis and release of dopamine were determined by measuring the rate of formation of 3H-H2O during the conversion of L3,5-3H-tyrosine into 3H-Dopa and the accumulation of newly synthesized 3H-dopamine in striatal slices and their incubating medium. Possible effects of the treatments on tyrosine striatal levels or tyrosine specific activity were also investigated. Dopamine synthesis rate was markedly accelerated 2.5 hrs after the acute injection of thioproperazine, but was equal to control levels 24 hrs later. The effects of thioproperazine and haloperidol were thus determined 2.5 and 24 hrs after an acute injection and following the last injection of a repeated daily treatment of 11 days. Dopamine synthesis and release were still markedly increased 2.5 hrs after the last injection of the subacute neuroleptic treatments when compared to controls, but these effects were less pronounced than those observed 2.5 hrs after an acute injection of either drug. Conversely, dopamine synthesis and release were significantly decreased 24 hrs after the last injection of the subacute neuroleptic treatments when compared to controls. Two hypotheses are proposed to explain the changes in dopamine synthesis induced by repeated treatments with neurolptics.

Animals↗
PubMedDate not supplied

Central serotonergic nerves project to the pial vessels of the brain.

Serotonin is strongly implicated in the aetiology of several cerebrovascular (circulatory) diseases, including stroke, migraine and vasospasm. Previous studies have suggested the existence of an indoleaminergic system of perivascular nerves in large cerebral arteries of the lamprey. In addition, some authors have observed that cerebral arteries (such as the vertebrobasilar system of the rabbit) and microvessels may take up serotonin and 5-hydroxytryptophan in various species. However, neither large cerebral arteries nor microvessels (primarily capillaries) directly control, or change, cerebral blood flow; as in other vascular beds, it is the arterioles and small arteries that are the major resistance elements. We report here on the presence of a central serotonergic innervation of pial arteries and arterioles in the rat, using immunocytochemical and neurochemical techniques. The fibres seem to have a central neuronal origin, emanating from both median and dorsal raphé nuclei. This perivascular serotonergic innervation may have a role both in the normal regulation of the cerebral circulation and in pathological conditions.

Animals↗
PubMedDate not supplied

[A specific domain (the omega 1 site) of the GABA(A) receptor may be implicated in the hypnotic effects of zolpidem].

Zolpidem (Stilnox) is a new hypnotic belonging to the imidazopyridine series. In animals, in contrast to the benzodiazepines which alter sleep architecture, zolpidem induces a physiological pattern of deep sleep. Zolpidem also differs from the benzodiazepines by its hypnoselective profile (its sedative effects are seen at doses much lower than those needed for anticonvulsant or myorelaxant effects). In this review, the authors analyze the hypothesis that the hypnoselective profile of zolpidem is linked to its interaction with a specific domain, the omega 1 site, of the GABAA receptor complex. This hypothesis is supported by: 1) the high selectivity of zolpidem for omega 1 as compared to omega 2 sites and its high intrinsic activity, 2) autoradiographic studies of the regional distribution of omega 1 and omega 2 sites in the human and non-human primate brains showing that omega 1 sites are located preferentially in sensorimotor cortical regions whereas omega 2 sites predominate in the limbic system and spinal cord. The selectivity of zolpidem for omega 1 sites could also account for the fact that in contrast to the benzodiazepines, this compound does not alter memory functions at hypnotic doses.

Animals↗