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B Scatton

Publications and source records attributed to B Scatton.

At least 235 records · Page 13Linked to original sources
PubMed1981

Differential changes in DOPAC levels in the hippocampal formation, septum and striatum of the rat induced by acute and repeated neuroleptic treatment.

Acute administration of haloperidol, sulpiride and chlorpromazine produces an elevation of hippocampal, septal and striatal DOPAC levels. The ED50 of haloperidol is similar in all areas but the maximal effect is much lower in the hippocampal formation than in septum and striatum. Repeated administration (11 days) of haloperidol causes a less pronounced increase (tolerance) in DOPAC levels in all regions investigated than acute treatment, the hippocampal formation being the most susceptible to this tolerance.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

[Biochemical mechanism of action of neuroleptics (author's transl)].

This review is devoted to the analysis of the mechanism of action of neuroleptics. The effects of these compounds on cerebral dopaminergic transmission and on the metabolism of various neurotransmitters are reviewed. Ample evidence derived from behavioral, clinical and biochemical studies indicates that a diminution of cerebral dopaminergic transmission (due to a blockade of dopaminergic receptors) probably accounts for the therapeutic activity (as well as some side effects) of neuroleptics. The tubero-infundibular dopaminergic system appears to play a major role in the neuroendocrine side effects of neuroleptics. Blockade of striatal dopaminergic transmission may probably be accounted for the extrapyramidal side effects induced by these drugs. As suggested by various biochemical data obtained in both animals and humans, the meso-cortico-limbic dopaminergic system appears to be the anatomical substrate of the antipsychotic action of neuroleptics. Recent results also suggest a modulatory influence of the frontal cortex on neuroleptic-induced extrapyramidal side effects. Finally, other cerebral neurotransmitters (noradrenaline, neuropeptides) might be involved in the mechanism of action of neuroleptic agents.

Animals↗
PubMed1980

Increase in striatal acetylcholine levels by GABAergic agents: dependence on corticostriatal neurons.

Surgical lesion of the corticostriatal projections almost totally reduced the ability of GABA agonist agents but not apomorphine to increase rat striatal ACh concentrations. This suggests that in intact rats, the GABAergic inhibition of striatal cholinergic neurons depends, at least in part, upon the corticostriatal (possibly glutamatergic) tract whereas the action of the dopaminergic pathway on cholinergic cells is independent of corticostriatal neurons.

Acetylcholine↗
PubMed1980

Origin of dopaminergic innervation of the rat hippocampal formation.

The origin of the dopaminergic afferents to the rat hippocampal formation has been investigated by measuring dopamine and DOPAC contents in this area after electrolytic or chemical lesion of the ventral tegmental area (A10) or substantia nigra (A9). The present study indicates that dopaminergic afferents to the hippocampal formation originate from the A10 and A9 dopaminergic cell groups. The 'anterior' hippocampal formation receives a major input from the A10 area whereas the 'posterior' hippocampal region receives dopaminergic afferents from both A9 and A10 cell groups. The dopaminergic afferents are entering the hippocampal region mainly through the dorsal route.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Effect of the new gamma-aminobutyric acid agonist SL 76 002 on striatal acetylcholine: relation to neuroleptic-induced extrapyramidal alterations.

A single injection of the new GABA receptor agonist SL 76 002 reduces the activity of striatal cholinergic neurons. Behaviorally, SL 76 002 (in large dose) potentiates haloperidol-induced catalepsy and antagonizes apomorphine-induced stereotypies. Repeated coadministration of haloperidol and SL 76 002 for 10 days does not affect the tolerance of the cholinergic system which is observed after haloperidol alone. In contrast, coadministration of the two drugs results in a marked prevention of the tolerance to the cataleptogenic action of haloperidol and of the increased sensitivity to apomorphine. It is suggested that (a) GABA mimetic medication inhibits striatal cholinergic transmission by a direct action on ACh cells; (b) behavioral effects resulting from alteration of dopaminergic transmission are--in contrast to the current view--not exclusively mediated by changes of cholinergic activity; (c) GABA affects striatal function via at least two mechanisms: by a direct input on, and independently from, both dopaminergic and cholinergic neurons; and (d) SL 76 002 possibly exerts a beneficial action in L-DOPA-induced abnormal movements in parkinsonian patients and neuroleptic-induced tardive dyskinesias.

Acetylcholine↗
PubMed1980

Antidopaminergic properties of yohimbine.

The effect of the alpha adrenoceptor blocking agent yohimbine on cerebral dopamine metabolism has been investigated in the rat. Yohimbine (1 to 10 mg/kg i.p.) increased in both striatum and limbic areas 1) homovanillic acid and dihydroxyphenylacetic acid levels, 2) tyrosine hydroxylase activity measured in vitro, 3) the in vivo accumulation of dihydroxyphenylalanine after NSD 1015 and 4) the rate of dopamine disappearance after alpha-methyl-p-tyrosine. The inability of clonidine to prevent the yohimbine-induced enhancement of striatal homovanillic acid levels in doses that antagonize the yohimbine-induced increase in noradrenaline turnover as well as the failure of other alpha adrenoceptor blocking agents (tolazoline, phentolamine and prazosin) to increase dopamine metabolism suggest that alpha adrenoceptors are not involved in the yohimbine-induced alteration of dopamine metabolism. Similarly to neuroleptic agents, yohimbine reduced striatal acetylcholine concentrations and counteracted the dopamine (10(-5) M)-induced inhibition of the potassium-evoked release of [3H]acetylcholine from slices of caudate nucleus. Yohimbine failed to further enhance striatal homovanillic acid levels in animals pretreated with a supramaximal dose of haloperidol. Moreover, in rats treated with haloperidol for 10 days, the effect of yohimbine on striatal homovanillic acid and acetylcholine levels was markedly reduced. It is concluded that yohimbine possesses postsynaptic dopamine receptor blocking properties in addition to its ability to inhibit alpha adrenergic receptors. The failure of yohimbine to affect dopamine-sensitive adenylate cyclase activity in striatal homogenates suggests an action of the compound on the D2 receptor.

Acetylcholine↗
PubMed1979

Dopamine metabolism, spiperone binding and adenylate cyclase activity in the adult rat hippocampus after ingrowth of dopaminergic neurones from embryonic implants.

The growth of dopamine (DA) neurones of rat embryonic mesencephalic brain tissue implanted close to the anterior part of the hippocampus of adult rats was studied by measuring the levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the host hippocampus. The hippocampal levels of DA and DOPAC reached maximal values 6 months after transplantation. The neuroleptic drug haloperidol evoked an increase in the levels of DOPAC. No evidence was found for the induction of DA-sensitive adenylate cyclase activity or of binding sites of [3H]spiperone. These results indicate that there is a substantial ingrowth of transplanted DA neurones into the host hippocampus, but no evidence was found for the development of functional contacts between the embryonic DA neurons and the host tissue.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

Definitive disruption of spatial delayed alternation in rats after lesions in the ventral mesencephalic tegmentum.

Prefrontal system dysfunction are revealed in rats in delayed response tasks. In view of the anatomical projections existing from the ventral mesencephalic tegmentum to the prefrontal system we have done this research in order to determine whether cognitive processes are impaired after mesencephalic lesions. Rats learned spatial delayed alternation in a T-maze. After acquisition they were randomly divided in two groups; the experimental group received lesions in the ventral mesencephalic tegmentum at the level of the A10 cell bodies. These lesions induced definitive disruption of the retention of the delayed alternation and the rats were unable to relearn the task. However, these animals were able to perform normally in an operant conditioning with food reinforcement indicating the specificity of the deficit observed with respect to the delayed alteration task. The possible modulating role of dopaminergic A10 neurones is hypothetized.

Animals↗
PubMed1979

Effects of clonidine, prazosin and phentolamine on heart rate and coronary sinus catecholamine concentration during cardioaccelerator nerve stimulation in spinal dogs.

1 In spinal dogs, continuous electrical stimulation of the cardioaccelerator nerve produced a transient rise in aortic blood pressure and a sustained increase in both heart rate and coronary sinus blood flow. The latter effects were accompanied by a significant elevation in the coronary sinus plasma noradrenaline concentration without significant changes in the levels of dopamine and adrenaline. The concentrations of the three catecholamines in thoracic aorta plasma were not significantly changed by cardioaccelerator nerve stimulation.2 Clonidine (20 mug/kg, i.v.), given during cardioaccelerator nerve stimulation, increased both mean aortic blood pressure and coronary sinus blood flow and decreased heart rate and coronary sinus venous plasma noradrenaline overflow.3 Phentolamine (0.3 mg/kg, i.v.) completely antagonized these effects of clonidine. Prazosin (0.3 mg/kg, i.v.) inhibited by only 43 and 38% the respective reductions in heart rate and noradrenaline overflow elicited by clonidine.4 On termination of cardioaccelerator stimulation (about 10 min after either prazosin or phentolamine), heart rate and coronary sinus noradrenaline overflow returned to control prestimulation levels.5 Phentolamine or prazosin, administered alone during stimulation of the cardioaccelerator nerve, increased heart rate and noradrenaline overflow into the coronary sinus plasma. However, intravenous phentolamine and prazosin, in contrast to desipramine (0.3 mg/kg, i.v.) or tyramine (1.0 mg, i.a.), failed to change the tachycardia resulting from the local administration of noradrenaline into the sinus node artery (i.a.).6 These results show that in spinal dogs the clonidine-induced reduction in heart rate (elevated by electrical stimulation of the cardioaccelerator nerve) is accompanied by a fall in the quantity of noradrenaline overflowing into the coronary sinus plasma. The latter effect is presumably the result of an action of clonidine on cardiac presynaptic alpha-adrenoceptors, the activation of which is followed by a reduction in the release of noradrenaline per nerve impulse. Phentolamine and prazosin are both antagonists of cardiac presynaptic alpha-adrenoceptors in spinal dogs, as suggested by their action against clonidine and by their positive chronotropic effect when administered during stimulation of the cardioaccelerator nerve.

Animals↗