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N Dusticier

Publications and source records attributed to N Dusticier.

At least 19 recordsLinked to original sources
PubMed1992

Intracerebroventricular administration of neuropeptide Y affects parameters of dopamine, glutamate and GABA activities in the rat striatum.

The effects of intracerebroventricular (ICV) injection of neuropeptide Y (NPY) on parameters of dopamine (DA), glutamate (Glu) and gamma-aminobutyric acid (GABA) activities were investigated in the rat striatum. NPY (1.17-4.70 nmol) induced a dose-dependent increase in the striatal endogenous DA release monitored in freely moving animals by means of a voltammetric method. Maximal increase was observed about one hour after the peptide injection. This result is consistent with the hypothesis that NPY may influence striatal DA turnover in a facilitatory manner by activating DA release. DA, DOPAC, Glu and GABA endogenous contents as well as 3H-Glu and 3H-GABA synaptosomal high affinity uptakes were examined one hour after NPY ICV administration at the same dose range in chloral hydrate-anesthetized animals. Depending on the NPY dose injected, opposite changes in Glu uptake were observed, suggesting that NPY has a bimodal influence on glutamatergic transmission. The Glu uptake rate increased markedly at 1.17 nmol NPY and decreased at 4.70 nmol, which may reflect an activation and an inhibition of the striatal Glu transmission, respectively. In parallel, the GABA uptake was found to decrease slightly at the higher doses of NPY tested, whereas no significant alteration of the striatal concentrations of either DA, DOPAC, Glu or GABA was observed. These results indicate that NPY may be involved in regulating the activity of nigral dopaminergic and cortical glutamatergic afferent pathways and that of intrinsic GABA neurons in the rat striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole) on striatal neurochemical markers in the rat, with special reference to the dopamine, choline, GABA and glutamate synaptosomal high affinity uptake systems.

Riluzole, a new compound with anticonvulsant properties, was found to induce a dose-dependent decrease in the uptake of 3H-dopamine, 3H-GABA and 3H-glutamate into striatal synaptosomes when added to the incubation medium or after in vivo administration, whereas an inhibition of 3H-choline uptake was detected only in the in vitro experiments. Interestingly, riluzole affected 3H-dopamine and 3H-glutamate uptake differentially since 3H-dopamine uptake was found to be more sensitive to the compound. Moreover, riluzole inhibited 3H-dopamine uptake competitively and 3H-glutamate uptake non-competitively, which further suggests that the action of the compound is selective. After in vivo injection, riluzole did not affect the striatal dopamine, DOPAC, serotonin, 5HIAA, glutamate, aspartate or GABA contents. Since this compound was previously reported to induce a decrease in the spontaneous release of glutamate, serotonin, dopamine and possibly acetylcholine, the hypothesis is put forward that riluzole may, at least at high concentrations, have general effects on the striatal nerve terminals affecting both the uptake and release processes. This action may be correlated with the recently identified blocking properties of the compound on the sodium channels, as previously shown for local anaesthetics.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Pyridostigmine-induced inhibition of blood acetylcholinesterase (AChE) and resulting effects on manual ocular tracking performance in the trained baboon.

A method was developed to determine the effects of pyridostigmine on sensory-motor control in baboons trained to perform visuo-oculo-manual tracking tasks. The performance was evaluated in terms of accuracy, maximum smooth pursuit velocity, and gain. Administration of pyridostigmine (0.4-0.7 mg/kg intramuscularly) induced a dose-related decrease in smooth pursuit performance which appeared 10 to 30 min after injection and lasted about 1 h. If the animal was allowed to track the target with its hand or to move the target itself, the smooth pursuit performance increased significantly, returning to near normal values. The movement of the hand was not altered. The effect of intramuscular injections of pyridostigmine (0.5 mg/kg) was studied on blood acetylcholinesterase activity in alert baboons. Maximum inhibition of about 60% of baseline activity was observed 10 min after pyridostigmine injection. Subsequently the activity slowly tended to return to control level. Three hours after drug administration, acetylcholinesterase activity inhibition was still 34.1% of control value. In the baboon, the time-course of acetylcholinesterase activity recovery after injection is similar to that recorded in human. The similarity of the time-course of blood acetylcholinesterase activity and changes in smooth pursuit performance suggests a causal relationship between the two factors. A further experiment showed that pyridostigmine administered per os at a dose normally used as a prophylactic against organophosphates does not significantly alter sensorimotor performance as evaluated at the oculomanual tracking system level. When compared to the literature, our results suggest that the baboon can be used as a human experimental analog for pharmacological studies such as the action of acetylcholinesterase inhibitors.

Acetylcholine↗
PubMed1990

Motor impairments and neurochemical changes after unilateral 6-hydroxydopamine lesion of the nigrostriatal dopaminergic system in monkeys.

Unilateral lesions of the nigrostriatal dopaminergic system were induced in five monkeys by intranigral injections of the neurotoxin 6-hydroxydopamine. Following the lesion, all monkeys showed a transient reluctance in using the contralateral forelimb, accompanied, in two monkeys by semi-flexed posture of the disabled forelimb. Three of the monkeys that had been conditioned to perform a visually triggered goal-directed arm movement, showed an increase in latency and duration of contralateral arm movements. Task performance recovered spontaneously to preoperative levels within four months in two monkeys despite significant reductions of endogenous dopamine and dihydroxyphenylacetic acid contents in the caudate nucleus, putamen and globus pallidus ipsilateral to the neurotoxic nigral injection. The third monkey exhibited a persistent increase in movement latency associated with a near complete loss of dopamine in both the putamen and the caudate nucleus. In all cases, an increase the dihydroxyphenyl-acetic acid to dopamine ratio was detected in the striatum and pallidum suggesting a compensatory increase in dopamine turnover in remaining intact dopaminergic nerve terminals. The level of serotonin was changed in all monkeys consisting of either a decrease or an increase, depending on the striatopallidal regions studied. Changes in choline acetyltransferase and glutamic acid decarboxylase activities in the same regions were only seen in some cases. The present results show that 6-hydroxydopamine-induced partial unilateral lesion of nigral dopaminergic neurons produced predominantly contralateral hypokinesia, accompanied by reductions of dopamine content in the ipsilateral striatum and pallidum. The use of this locally applied neurotoxin appears to be a suitable method for investigating neurophysiological mechanisms underlying hypokinesia since deficits in both initiating and executing movements can be expressed independently of other behavioral symptoms. The results show more persistent deficits in starting movements than in their execution and thus suggest that motor initiation is more dependent upon the functional integrity of the nigrostriatal dopamine system than movement completion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Modulatory effect of dopamine on high-affinity glutamate uptake in the rat striatum.

In vivo electrical stimulation of the frontal cortical areas was found to enhance sodium-dependent high-affinity glutamate uptake (HAGU) measured in rat striatal homogenates. This activating effect was counteracted by in vivo administration of apomorphine and by in vitro addition of dopamine (DA; 10(-8) M) in the incubation medium, and potentiated by in vivo haloperidol administration. At the doses used, the dopaminergic compounds had no effect on basal HAGU. alpha-Methylparatyrosine pretreatment was found to enhance slightly basal HAGU as well as the activating effects of cortical stimulation. Interestingly enough, lesion of dopaminergic neurons by substantia nigra injection of 6-hydroxydopamine (6-OHDA) did not cause any significant change either in basal HAGU or in the effect of cortical stimulation. Measurement of DA effects in vitro in experiments combined with in vivo manipulations of the dopaminergic nigrostriatal and corticostriatal systems showed that the capacity of DA to inhibit striatal HAGU depends directly on the level of the uptake activation reached over basal value. These results suggest that under physiological conditions, the dopaminergic nigrostriatal pathway exerts a modulatory presynaptic action on corticostriatal glutamatergic transmission, counteracting increasing glutamatergic activity. In the case of chronic DA depletion induced by 6-OHDA, striatal adaptations may occur modifying the mechanisms acting at corticostriatal nerve terminal level.

Animals↗
PubMed1985

Changes in choline acetyltransferase, glutamic acid decarboxylase, high-affinity glutamate uptake and dopaminergic activity induced by kainic acid lesion of the thalamostriatal neurons.

Kainic acid lesion of the 'centre médian'-parafascicular complex of the thalamus inducing a degeneration of the thalamostriatal neurons was followed by a decrease in choline acetyltransferase (ChAT) in the rostral part of the striatum in the rat. This decrease in ChAT was concomitant with an increase in glutamate decarboxylase, high-affinity glutamate uptake and apparent dopamine turnover. These results suggest that the thalamostriatal partly cholinergic input exerts a powerful control over GABAergic, glutamatergic and dopaminergic neurons in the basal ganglia.

Animals↗
PubMed1985

Effects of pyroglutamic acid on corticostriatal glutamatergic transmission.

The effects of L-pyroglutamic acid, a molecule structurally derived from L-glutamic acid (Glu), were measured on the high affinity of uptake of glutamic acid from striatal synaptosomes of the rat and on the binding of [L-3H]glutamic acid to striatal membranes. The results showed a competitive inhibition of the high affinity transport of glutamic acid by L-pyroglutamic acid in vitro with no effect on the uptake of gamma-aminobutyric acid (GABA). An inhibition of the binding of [L-3H]glutamic acid to striatal membranes was also detected. Significant high affinity uptake of [L-3H]pyroglutamic acid was evident in synaptosomes from the striatum. A regional distribution study of the uptake processes for [L-3H]glutamic acid and [L-3H]pyroglutamic acid in different areas of the brain showed a similar distribution, suggesting that an uptake of [L-3H]pyroglutamic acid, although weak, occurs in glutamatergic nerve terminals. This proposal was further reinforced by measuring the effects of a large cortical lesion involving frontal and parietal areas on the uptake of [L-3H]glutamic acid and [L-3H]pyroglutamic acid in synaptosomes from the striatum. The results showed a large decrease in the uptake processes of both labelled molecules showing that the uptake of [L-3H]pyroglutamic acid, as for glutamic acid mainly occurred in corticostriatal nerve terminals, although other uptake sites are not excluded.

Animals↗
PubMed1984

High affinity glutamate uptake in the red nucleus and ventrolateral thalamus after lesion of the cerebellum in the adult cat: biochemical evidence for functional changes in the deafferented structures.

High affinity glutamate uptake (HAGU) was measured within the red nucleus (RN) and the ventrolateral thalamic area in intact adult cats and in animals which had undergone a large hemicerebellectomy 8 to 21 days before. In the side contralateral to the lesion, results show two types of changes in HAGU: 1. In the caudal parts of the RN and the ventrolateral thalamic nucleus (VL), a strong HAGU decrease was demonstrated suggesting some cerebellorubral and cerebellothalamic fibres use glutamate (Glu) as their neurotransmitter. 2. In the rostral parts of the RN and the VL, an increase in HAGU was detected. This increase was particularly large at thalamic level, which led us to perform a kinetic analysis of the uptake system. Results show that the increase observed in HAGU is related in the thalamic area to an increased affinity of the transport sites for Glu. The mechanism of the HAGU increase measured in the rostral VL after cerebellectomy was further investigated in the presence of acetylcholine (ACh) which we have previously shown to be possibly involved in the neurotransmission of some cerebellothalamic and cerebellorubral fibres. ACh was shown to exert an inhibitory effect on HAGU in the control situation. Decrease in affinity of the transport sites for Glu induced by ACh was more pronounced when HAGU was enhanced as a consequence of the cerebellar lesion. We hypothesized that the cerebellectomy enhances the activity of nerve terminals which take up Glu in the VL and that we have shown to be mainly related to corticothalamic neurons. The basic mechanism involved in this activation could be the withdrawal of presynaptic inhibitory controls on corticothalamic fibres due to the removal of the putative cholinergic cerebellar input. This hypothesis was extended to the RN where previous electrophysiological and anatomical studies have suggested that the cerebellar lesion induces a sprouting of corticorubral nerve terminals. The increase in HAGU in response to the cerebellar lesion could constitute an adaptive mechanism by which the CNS may compensate for the loss of the excitatory cerebellar input to the RN and thalamic neurons by increasing the corticofugal transmission.

Animals↗
PubMed1983

Presynaptic dopaminergic control of high affinity glutamate uptake in the striatum.

The high affinity glutamate uptake (HAGU) was measured in homogenates obtained from striata of control rats and animals submitted to electrical stimulation of the frontal cortical areas. Results show that the stimulation of the corticostriatal neurons induces an activation of the uptake of glutamate (Glu) in the striatum resulting from an increase in the affinity of the transport site for Glu. In other experiments we have obtained evidence that, when stimulated, presumed dopaminergic receptors can inhibit HAGU. The dopaminergic antagonist haloperidol was shown not to influence that basal Glu uptake but this neuroleptic highly potentiates the excitatory effects of cortical stimulations. The nigrostriatal dopaminergic pathway may exert a modulatory action on the corticostriatal glutamatergic neurons as it counteracts increasing glutamatergic activity.

Afferent Pathways↗
PubMed1983

In vitro radioautographic study of the monoaminergic innervation of cat red nucleus. Identification of serotoninergic terminals.

This study emphasizes the existence of a dense plexus of serotoninergic nerve terminals having specifically accumulated tritiated serotonin in vitro in the red nucleus of cat. These terminals innervate the whole rostrocaudal extension of the nucleus, being frequently in close apposition to the cell bodies and proximal dendrites of magnocellular neurons in its caudal part. A possible involvement of this serotoninergic input in the modulation of cerebello-rubro-spinal activity is proposed.

Animals↗
PubMed1983

Topographic changes in high-affinity glutamate uptake in the cat red nucleus, substantia nigra, thalamus, and caudate nucleus after lesions of sensorimotor cortical areas.

The distribution of presumed glutamatergic projections from sensorimotor cortical areas to the red nucleus (RN), the substantia nigra (SN), the ventrolateral thalamic complex, and the caudate nucleus (CN) was investigated in the cat. For this purpose, the changes in the sodium-dependent high-affinity glutamate uptake (HAGU) rate were measured in homogenates of tissue microdissected from various parts of these subcortical structures after chronic surgical ablation of sensorimotor cortical areas. After 8 to 10 days survival, significant reductions in HAGU activity were noted in the structures studied on the side ipsilateral to the operated cortex. Within each structure, various quantitative or qualitative changes were observed. Higher decreases in HAGU activity were found in the caudal part of the RN, the ventrolateral thalamic nucleus, and the dorsolateral part of the CN than in the other parts of these structures. The lateral part of the SN showed a large decrease in HAGU rate and its medial part a small but significant increase. Referring to the anatomic data concerning the organization of cortical projections from sensorimotor areas to the structures studied, it was shown that our results support the view that glutamate could act as a neurotransmitter along various corticosubcortical pathways.

Animals↗
PubMed1983

Glutamate uptake, glutamate decarboxylase and choline acetyltransferase in subcortical areas after sensorimotor cortical ablations in the cat.

High affinity glutamate uptake (HAGU), glutamate decarboxylase (GAD) and choline acetyltransferase (CAT) activities were measured from subcortical nuclei in the cat brain after ipsilateral ablation of the sensorimotor cortex. Results showed a drop in HAGU in all the structures assayed except the subthalamic nucleus. These changes in HAGU are generally accompanied by a decrease in GAD while CAT is unaffected. However, in the red nucleus the drop in HAGU is concomitant to an increase in GAD and CAT. In the subthalamic nucleus HAGU and CAT are increased while GAD is decreased. These results are consistent with the concept that most corticofugal fibres to subcortical structures use glutamate as their neurotransmitter. Results concerning GAD suggest that GABAergic subcortical neurons are under a cortical influence. This influence seems to be weak on cholinergic neurons.

Animals↗
PubMed1982

Inhibitory effects of dopamine on high affinity glutamate uptake from rat striatum.

The role of dopamine (DA) input on the activity of glutamate neurons was investigated on rat striatal and cortical tissue using the measurement of sodium-dependent high affinity glutamate uptake (HAGU) as an index. Incubation of the tissue in the presence of DA, apomorphine or bromocriptine produced marked inhibition of 3H-glutamate uptake from rat striatal homogenates. No change occurred with samples from the frontal cortex. Dopaminergic inhibition of HAGU in striatal homogenates was shown to be reversed in the presence of haloperidol or domperidone which act by blocking dopaminergic receptor sites. These results are consistent with the existence of an inhibitory control of the neuronal activity of the glutamatergic neurons in the striatum by the nigro-striatal dopaminergic input. The effects could be due to the activation of D2-like DA receptors located at pre-synaptic levels on cortico-striatal glutamatergic nerve endings.

Afferent Pathways↗
PubMed1982

Effect of superficial radial nerve stimulation on the activity of nigro-striatal dopaminergic neurons in the cat: role of cutaneous sensory input.

The release of 3H-dopamine (DA) continuously synthesized from 3H-tyrosine was measured in the caudate nucleus (CN) and in the substantia nigra (SN) in both sides of the brain during electrical stimulation of the superficial radial nerve in cats lightly anaesthetized with halothane. Use of appropriate electrophysiologically controlled stimulation led to selective activation of low threshold afferent fibers whereas high stimulation activated all cutaneous afferents. Results showed that low threshold fiber activation induced a decreased dopaminergic activity in CN contralateral to nerve stimulation and a concomitant increase in dopaminergic activity on the ipsilateral side. Stimulation of group I and threshold stimulation of group II afferent fibers induced changes in the release of 3H-DA mainly on the contralateral CN and SN and in the ipsilateral CH. High stimulation was followed by a general increase of the neurotransmitter release in the four structures. This shows that the nigro-striatal dopaminergic neurons are mainly--if not exclusively--controlled by cutaneous sensory inputs. This control, primarily inhibitory in the side contralateral to the stimulation, seems rather non-specific when high threshold cutaneous fibers are also activated. Such activations could contribute to reestablish sufficient release of DA when the dopaminergic function is impaired as in Parkinson's disease.

Animals↗
PubMed1981

Increased glutamate decarboxylase activity in the red nucleus of the adult cat after cerebellar lesions.

Glutamate decarboxylase (GAD)activity, a marker for GABAergic structures, was studied in the cat red nucleus. GAD is more concentrated in the rostral than in the caudal third of the structure. GAD levels were measured after chronic unilateral lesions of the cerebellum. Destruction of the dentate area and of the nucleus interpositus induced increases of GAD in the contralateral but not in the ipsilateral red nucleus. Similar changes also occurred in the denervated nucleus ventralis lateralis (VL) and nucleus ventralis anterior (VA) of the thalamus. Results show that loss of the excitatory cerebellar input could lead to changes in inhibitory GABAergic nerve terminals. This increase may be induced transsynaptically within existing neurons or, more likely, additional GAD-containing nerve terminals may be formed by axonal sprouting.

Afferent Pathways↗
PubMed1981

Decrease in choline acetyltransferase and in high affinity glutamate uptake in the red nucleus of the cat after cerebellar lesions.

Acetylcholine (ACh) is suggested to be a neurotransmitter in cerebellothalamic and cerebellorubral fibres. We therefore measured choline acetyltransferase (CAT) activity in the cat red nucleus after lesion of the contralateral cerebellum. Decreased CAT activity was obtained (-37%), specifically localized in the red nucleus and particularly in its rostral parvocellular part. Since the red nucleus of the cat displays rather low CAT levels, the possible cholinergic input seems not be sufficient to explain the powerful action of the cerebellum on red nucleus magnocellular neurons. As glutamic acid (Glu) may be the neurotransmitter of many excitatory systems in the brain, we measured high affinity Glu uptake in the red nucleus after lesions of the contralateral cerebellum. Results showed a decreased (-35%) Glu activity restricted to the red nucleus and particularly in its caudal magnocellular part.

Animals↗
PubMed1981

Glutamate decarboxylase distribution in discrete motor nuclei in the cat brain.

The distribution of activity of glutamate decarboxylase (GAD), the enzyme synthesising gamma-aminobutyric acid (GABA), was measured in the cat brain by means of microdissection of the structures from frozen slices and a radioisotopic assay for the enzyme. About 20 cerebral regions were chosen for study because of their role in sensorimotor integration. GAD presented an uneven distribution among these areas. Highest activities were found in the basal ganglia, particularly in the substantia nigra and in the globus pallidus, and to a lesser extent in the cerebellum. Relatively low levels of the enzyme were found in the thalamus and in the cerebral motor cortex. Special detailed studies were made in the caudate nucleus, the substantia nigra, and in the red nucleus for the purpose of defining the intranuclear distribution of their GABAergic innervation. There were only small differences in the rostro-caudal distribution of the enzyme in the head of the caudate nucleus but GAD activity was higher in the ventral than in the dorsal part of the structure. In the substantia nigra, GAD activity was high in both the medial and intermediate thirds of the structure. The GAD activity decreased from the caudal to the rostral part of the nucleus. GAD levels were lower in the caudal part of the red nucleus than in the rostral part. These results indicate that GABA would be present as a putative neurotransmitter in many motor nuclei of the cat brain. In view of the general inhibitory action of this amino acid, this could be related to the presence of inhibitory responses widely distributed in these nuclei as identified by mean of electrophysiological studies. The origin of these GABAergic innervations in many cases remains to be determined.

Animals↗