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Biomedical subjects

M J Besson

Publications and source records attributed to M J Besson.

At least 37 records · Page 2Linked to original sources
PubMed1986

Supernumerary locus coeruleus neurons as a determinant of inherited epilepsy in the convulsive mutant mouse quaking.

In quaking mice (a genetic model of epilepsy with an increased number of noradrenergic neurons) bilateral electrolytic coagulation of locus coeruleus (LC) in adult mice inhibited the convulsions elicited by somatic stimulations while neonatal 6-hydroxydopamine (6-OHDA) treatment remained ineffective upon the convulsions. Biochemical effects of the two treatments differed only in the brainstem where electrolytic lesion decreased while 6-OHDA treatment increased noradrenaline (NA) and 3-methoxy 4-hydroxyphenylethyleneglycol (MHPG) levels. Our results suggest that supernumerary LC neurons mediate the convulsions of the mutants through an action presumably restricted to the brainstem.

Animals↗
PubMed1986

In vivo release of [3H]gamma-aminobutyric acid in the rat neostriatum--I. Characterization and topographical heterogeneity of the effects of dopaminergic and cholinergic agents.

The release of [3H]gamma-aminobutyric acid continuously synthesized from [3H]glutamine was studied in the striatum of halothane-anaesthetized rats superfused with a push-pull cannula. The levels of spontaneously released [3H]GABA were identical in all striatal regions examined, but were found to be higher at the junction between the striatum and the globus pallidus. Superfusion with a medium enriched in K+ ions induced a concentration-dependent increase in [3H]GABA release. Superfusion with a Ca2+-free medium did not affect the spontaneous outflow of [3H]GABA but sharply reduced the release of [3H]GABA evoked by 30 mM K+. Locally applied tetrodotoxin (50 microM) decreased slightly the spontaneous release of [3H]GABA (-22%). When acetylcholine (50 or 500 microM) was added to a superfusion medium containing eserine (50 microM), the spontaneous release of [3H]GABA was enhanced in the ventral but not in the dorsal region of the striatum. The local application of 2,3,4,5-tetrahydro, 7,8,-dihydroxy, 1-phenyl, 1-H, 3-benzazepine (10 microM), a dopaminergic agonist acting preferentially on D1 receptors increased the release of [3H]GABA in the dorsal striatum (+32%) but decreased it slightly (-19%) in the ventral striatum. 3-(2-(N-3 hydroxyphenylethyl)N-propylamino)ethyl-phenol (50 microM), a preferential D2 receptor agonist, decreased [3H]GABA release when it was applied dorsally (-23%) but not ventrally in the striatum. It is concluded that the regulation of the release of [3H]GABA by acetylcholine and dopaminergic drugs is different in the dorsal and ventral regions of the striatum. These differences may be related to the existence of subpopulations of GABA neurons and may well have functional implications as suggested by behavioural studies.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

In vivo release of [3H]gamma-aminobutyric acid in the rat neostriatum--II. Opposing effects of D1 and D2 dopamine receptor stimulation in the dorsal caudate putamen.

The effects of several dopaminergic agonists and antagonists on the spontaneous release of [3H]gamma-aminobutyric acid were investigated in the dorsal striatum of halothane-anaesthetized rats. A push-pull cannula was implanted and the tissue was superfused continuously with a physiological medium containing [3H]glutamine, the precursor of [3H]GABA. Drugs were added to the superfusion medium. 2-Amino,6,7-dihydroxy,1,2,3,4-tetrahydro-naphtalene (ADTN, a mixed D1 and D2 receptor agonist) and D-amphetamine (a drug that enhances the release of endogenous dopamine) increased the release of 3H-GABA. The effect of ADTN was blocked by a D1 antagonist [R-(+),8-chloro, 7-hydroxy,2,3,4,5-tetrahydro,3-methyl,5-phenyl,1-H,3-benzazepine (SCH 23390)] but not by a D2 antagonist (S-sulpiride). Furthermore the stimulation of D1 receptors either by 2,3,4,5-tetrahydro,7,8-dihydroxy,1-phenyl,1-H,3-benzazepine or by D-amphetamine in the presence of S-sulpiride also enhanced the release of [3H]GABA. On the other hand, a selective D2 receptor agonist (3-(2-(N-3-hydroxy-phenylethyl)N-propylamino)ethyl-phenol) decreased the release of [3H]GABA. This effect was blocked in the presence of S-sulpiride. By itself the D1 receptor antagonist (SCH 23390) decreased the release of [3H]GABA whereas the D2 receptor antagonist (S-sulpiride) had no effect. It was concluded that stimulation of D1 and D2 receptors produces opposing effects on the spontaneous release of [3H]GABA in the dorsal striatum. Stimulation of D1 receptors facilitates the release of [3H]GABA whilst stimulation of D2 receptors inhibits it. The effect of D1 receptor stimulation appears to be predominant, and endogenous dopamine may activate tonically the release of GABA through these receptors in our experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Release of newly synthesized 3H-dopamine in the striatum: an adaptation of the push-pull cannula method to awake restrained and anesthetized rats.

The release of newly synthesized 3H-dopamine (3H-DA) was measured in the rat striatum superfused, through a push-pull cannula, with a physiological medium enriched in 3H-tyrosine. The level of spontaneous 3H-DA release was dependent on the topographical localisation of the cannula in the striatum (anterior parts displayed higher levels than posterior ones) and on the anesthetic state (halothane anesthetized rats demonstrated higher levels than awake ones). Inhibition of DA inactivation processes by local application of benztropine (a DA reuptake inhibitor, 10(-6) M) or by IV administration of pargyline (a MAO inhibitor, 100 mg/kg) enhanced the detectable outflow of 3H-DA from the striatum in both halothane anesthetized and awake rats. Local application of D-amphetamine (10(-5) M) or acetylcholine (5 X 10(-5) M) in the presence of eserine (5 X 10(-5) M) evoked respectively a fivefold and a 30% increase in spontaneous 3H-DA release in halothane anesthetized rats. Inhibition of the firing of dopaminergic neurons by IV injection of gamma-hydroxybutyrate (400 mg/kg) produced a 30% decrease in striatal 3H-DA release. The present results demonstrate that the push-pull cannula method is suitable for the study of DA release in both the anesthetized and the awake rat.

Acetylcholine↗
PubMed1986

Apomorphine and haloperidol effects on striatal 3H-dopamine release in anesthetized, awake restrained and freely moving rats.

The ability of apomorphine (APO) and haloperidol (HAL) to affect the spontaneous release of newly synthesized 3H-DA in the striatum was studied in halothane anesthetized, gallamine paralyzed, awake restrained and freely moving rats. The striatum was continuously superfused through a push-pull cannula with a physiological medium enriched in 3H-tyrosine. Basal levels of 3H-DA release were different in the four experimental models: highest in halothane anesthetized rats, intermediate in awake restrained and gallamine treated rats and lowest in freely moving rats. In all experimental models IV or SC injection of APO (1 mg/kg) inhibited the release of 3H-DA (30-50%) from 15 to 90 min following its administration. In awake restrained and freely moving rats, stereotyped behaviour was observed for one hour following the APO injection. In halothane anesthetized rats the inhibitory effect of APO on 3H-DA release was prevented by pretreatment with HAL (2 mg/kg IV). Injection of HAL (2 mg/kg IV or SC) failed to enhance the release of 3H-DA in anesthetized and awake restrained rats, whilst a long-lasting increase in 3H-DA release was observed in gallamine treated and freely moving animals (55% and 120% respectively). However, catalepsy was observed in both restrained and freely moving rats. It is concluded that the modifications of 3H-DA release produced by HAL but not those produced by APO are dependent on the experimental model used, a fact possibly related to the different sites of action of these two drugs.

Anesthesia, General↗
PubMed1986

In vivo release of endogenous amino acids from the rat striatum: further evidence for a role of glutamate and aspartate in corticostriatal neurotransmission.

By means of the push-pull cannula method, the outflow of endogenous amino acids was studied in the striatum of halothane-anesthetized rats. Addition of K+ ions (30 mM for 4 min) to the superfusion fluid increased the release of aspartate (+116%), glutamate (+217%), taurine (+109%), and gamma-aminobutyric acid (GABA) (+429%) whereas a prolonged decrease in the outflow of glutamine (-28%) and a delayed reduction in the efflux of tyrosine (-25%) were observed. In the absence of Ca2+, the K+-induced release of aspartate, glutamate, and GABA was blocked whereas the K+-induced release of taurine was still present. Under these conditions, the decrease in glutamine efflux was reduced and that of tyrosine was abolished. Local application of tetrodotoxin (5 microM) decreased only the outflow of glutamate (-25%). One week following lesion of the ipsilateral sensorimotor cortex the spontaneous outflow of glutamine and of tyrosine was enhanced. Despite the lack of change in their spontaneous outflow, the K+-evoked release of aspartate and glutamate was less pronounced in lesioned than in control animals, whereas the K+-evoked changes in GABA and glutamine efflux were not modified. Our data indicate that the push-pull cannula method is a reliable approach for the study of the in vivo release of endogenous amino acids. In addition, they provide further evidence for a role for glutamate and aspartate as neurotransmitters of corticostriatal neurons.

Amino Acids↗
PubMed1986

[Effect of lesions of the ventromedial nucleus of the thalamus on cerebral metabolism: experimental study in the rat using the 14C-deoxyglucose method].

Local cerebral glucose utilization (LCGU) was studied quantitatively in awake rats one week and one month following unilateral electrolytic lesion of the ventromedial thalamic nucleus (VM). Significant decrease in LCGU were observed in the ipsilateral cortex as well as in some contralateral cortical areas and bilateral subcortical structures. The modifications by the VM lesion, of the metabolic activations induced by electrical stimulation of substantia nigra pars reticulata (SNR, main afference of the VM) were investigated also. Results suggest that VM is an important relay nucleus on the pathways directed from one SNR towards ipsilateral corticostriatal system and contralateral thalamus and basal ganglia. Finally, one month following the VM lesion a recovery of metabolic activations induced by SNR stimulation was observed whereas basal glucose consumption remained decreased.

Animals↗
PubMed1985

Bilateral cerebral metabolic alterations following lesion of the ventromedial thalamic nucleus: mapping by the 14C-deoxyglucose method in conscious rats.

The functional role of the ventromedial thalamic nucleus (VM) was investigated by means of the quantitative autoradiographic 14C-deoxyglucose method. Local cerebral glucose utilization (LCGU) was measured bilaterally in 53 discrete brain areas of conscious rats 1 week and 1 month following electrolytic lesion of the VM. There was no difference observed in the LCGU values between the two groups of lesioned animals. In the VM-lesioned rats glucose consumption was decreased in several ipsilateral (pre-frontal, frontal, cingulate, sensorimotor, visual) and in some contralateral (cingulate, sensorimotor, visual) cortical areas. Furthermore, LCGU values were depressed bilaterally in the striatum, hippocampus, dentate gyrus, substantia nigra compacta, superficial layers of the superior colliculus, oculomotor complex, and cerebellar dentate nuclei. Glucose utilization was diminished also in the deep layers of the superior colliculus and in the fastigial nucleus ipsilateral to the lesion. Within the thalamus, glucose metabolism was decreased in several nuclei either bilaterally (reticular, intralaminar, paralamellar mediodorsal) or ipsilaterally (lateroposterior, ventrobasal, ventrolateral, ventroanterior, and medioventral) to the lesion. A significant correlation between the percentage of injured VM and the regional metabolic depression was demonstrated in the areas displaying the most pronounced decrease in LCGU. These results support a widespread influence of the VM on brain function extending beyond the limits of purely motor systems and reveal the consequences of a unilateral lesion of the thalamus on metabolic activity in several contralateral structures.

Animals↗
PubMed1985

Local cerebral metabolic effects induced by nigral stimulation following ventromedial thalamic lesions. II: Sensory motor, reticular and limbic systems.

The involvement of the ventromedial thalamic nucleus (VM) in mediating the local cerebral metabolic effects induced by unilateral substantia nigra (SN) electrical stimulation was investigated in the awake rat. Local cerebral glucose utilization (LCGU) was measured during ipsilateral SN-stimulation in VM-intact rats as well as in animals bearing 8 or 30 days old electrolytic VM-lesions, using the 14C-deoxyglucose quantitative autoradiographic method. In VM-intact rats, SN-stimulation enhanced LCGU in several bilateral components of the sensory motor, reticular, and limbic systems despite the lack of direct anatomical connections. Almost all these metabolic activations were no longer apparent one week following VM-lesion. In contrast, one month after the VM-injury, the above activations reappeared even more dramatically than in VM-intact animals especially on the contralateral side. It is concluded that SN-stimulation activates several brain regions of both hemispheres beyond the traditional motor areas, the role of the VM in mediating these activations is crucial, and the plasticity of the adult CNS allows for recovery of metabolic responsiveness in a disturbed system.

Afferent Pathways↗
PubMed1979

Topographical distribution of substance P in the cat substantia nigra.

The substance P (SP) content in cat substantia nigra (SN) was estimated by radioimmunoassay in microdiscs punched on successive frontal sections. Only slight differences were seen in the regional distribution of SP within the SN. The highest content was found in the pars reticulata (20.7 pmol/mg protein) which was two times higher than in the pars compacta and pars lateralis. Identical results were found in the right and left part of the SN. Out of this area, as pedunculus cerebri and zona incerta, very low concentrations were detected.

Animals↗
PubMed1979

Chronic methods to study the release of catecholamines from the neostriatum in nonanaesthetized monkeys (Macaca mulatta).

The present report describes two methods allowing the chronic collection of catecholamine (CA) released from the neostriatum in the nonanaesthetized monkey (Macaca mulatta). In both methods the monkeys were placed in a restraining chair. Indwelling electrodes allowed the correlation of behavioural observations with polygraphic recordings. The first method uses a special superfusing cup permanently implanted on the lateral surface of the caudate nucleus, which permits the demonstration of spontaneous and D-amphetamine-induced release of (3H)-dopamine (DA) newly synthesized from L-(3,5-3H)-tyrosine over a period of six days. In the second method the collection of unlabelled CA is carried out by a localized ventricular perfusion. A radio-enzymatic estimation enabled the measurement of unlabelled DA and noradrenaline. With this second method the animals were kept for 25 to 30 days.

Amphetamine↗
PubMed1979

Role of various amino acids on the modulation of dopamine release from nigro-striatal dopaminergic neurones.

The effects of various transmitter amino-acids on the striatal release of 3H-dopamine (3H-DA) were investigated both in vivo in cat and in vitro in rat striatal slices. When applied to the substantia nigra of the anaesthetized cat by means of a push-pull cannula, GABA induced an increase followed by a transient decrease of 3H-DA release in the ipsilateral caudate nucleus; glycine reduced 3H-DA release under similar experimental conditions. When added to the superfusion medium of rat striatal slices, GABA, glutamate and glycine increased the release of the newly synthetized 3H-DA, suggesting that these amino-acids are also directly or indirectly involved in the presynaptic modulation of striatal DA release.

Animals↗
PubMed1977

Involvement of cholinergic presynaptic receptors of nicotinic and muscarinic types in the control of the spontaneous release of dopamine from striatal dopaminergic terminals in the rat.

Rat striatal slices (two) were superfused continuously with L-3,5-3H tyrosine and 3H-dopamine (3H-DA) release was estimated in serial fractions of superfusates. The spontaneous release of 3H-DA was reduced by about 50% when slices were superfused with a calcium-free medium containing ethylene glycol bis (beta-aminoethyl ether)- N,N'-tetraacetic acid (EGTA) (10(-4) M) or with a medium containg tetrodotoxin (5 x 10(-7) M). These effects were not related to a change in 3H-DA synthesis since the rate of L-3,5-3H tyrosine hydroxylation, as measured by 3H-H2O formation was not significantly reduced. Acetylcholine (ACh) (10(-5) M) stimulated the release of 3H-DA (about 100%). This effect was abolished in the absence of calcium; it was partially blocked by pempidine (10(-5) M), atropine (10(-6) M) or scopolamine (10(-5), 10(-6) M). Oxotremorine (10(-5) M) enhanced 3H-DA release but to a lesser extent (60%) than ACh (10(-5) M); its action was completely blocked by atropine (10(-6) M) and unaffected by pempidine (10(-5) M). The ACh- (10(-5) M) and oxotremorine- (10(-5) M) stimulatine effects on 3H-DA spontaneous release were still detected in slices superfused in the presence of tetrodotoxin (5 x 10(-7) M). In the presence of the neurotoxin, the effect of ACh (10(-5) M) was significantly reduced by pempidine (10(-5) M) and the effect of oxotremorine (10(-5) M) was blocked by atropine (10(-6) M). These results suggest the presence of cholinergic presynaptic receptors of the nicotinic and muscarinic types on striatal dopaminergic terminals.

Acetylcholine↗
PubMed1976

Radioautographic study of in vivo incorporation of 3H-monoamines in the cat caudate nucleus: identification of serotoninergic fibers.

The localization of radioactivity was examined in the caudate nucleus of the cat, treated with an MAO inhibitor, following local superfusion of the ventricular surface of the structure with low concentration of 3H-catecholamines or [3H]5-HT. The caudate nucleus was superfused continuously from 30 to 240 min using a cup technique. Light microscope or high resolution radioautographs revealed: (1) a rather diffuse incorporation of 3H-catecholamines under the subependymal region which could be hardly attributed to a specific population of nerve terminals. A loose binding of 3H-catecholamines into dopaminergic terminals could be involved in this effect. (2) An intense and selective uptake of [3H]5-HT in fine scarce varicose nerve fibers localized in the ventricle as in the subependymal layer and in the neuropil of the nucleus. The labeled fibers contained numerous round or elongated large granular vesicles of 80-120 nm and exhibited only very few synaptic contacts suggesting a possible extrasynaptic liberation of 5-HT.

Animals↗