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G Chouvet

Publications and source records attributed to G Chouvet.

At least 37 records · Page 2Linked to original sources
PubMed1993

Tonic activation of NMDA receptors causes spontaneous burst discharge of rat midbrain dopamine neurons in vivo.

Midbrain dopamine neurons in vivo discharge in a single-spike firing pattern or in a burst-firing pattern. Such activity in vivo strikingly contrasts with the pacemaker activity of the same dopamine neurons recorded in vitro. We have recently shown that burst activity in vivo of midbrain dopamine neurons is due to the local activation of excitatory amino acid receptors, as microapplication of the broad-spectrum antagonist of excitatory amino acids, kynurenic acid, strongly regularized the spontaneous firing pattern of these dopamine neurons. In the present study, we investigated which subtypes of excitatory amino acid receptors are involved in the burst-firing of midbrain dopamine neurons in chloral hydrate-anaesthetized rats, iontophoretic or pressure microejections of 6-cyano, 7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (NMDA) receptor antagonist, did not alter the spontaneous burst firing of dopamine neurons (n = 36). In contrast, similar ejections of (+-)2-amino,5-phosphonopentanoic acid (AP-5), a specific antagonist at NMDA receptors, markedly regularized the firing pattern by reducing the occurrence of bursts (n = 52). In addition, iontophoretic ejections of NMDA, but not kainate or quisqualate, elicited a discharge of these dopamine neurons in bursts (n = 20, 12 and 14, respectively). These data suggest that burst-firing of midbrain dopamine neurons in vivo results from the tonic activation of NMDA receptors by endogenous excitatory amino acids. In view of the critical dependency of catecholamine release on the discharge pattern of source neurons, excitatory amino acid inputs to midbrain dopamine neurons may constitute a major physiological substrate in the control of the dopamine level in target areas.

Animals↗
PubMed1993

The 5-HT1A receptor selective ligands, (R)-8-OH-DPAT and (S)-UH-301, differentially affect the activity of midbrain dopamine neurons.

The effects of the selective 5-HT1A receptor agonist (R)-8-hydroxy-2(di-n-propylamino)tetralin [(R)-8-OH-DPAT] and the novel 5-HT1A antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)-tetralin [(S)-UH-301] were studied with regard to the firing pattern of single mesencephalic dopamine (DA) neurons with extracellular recording techniques in chloral hydrate anesthetized male rats. Neuronal activity was studied with respect to firing rate, burst firing and regularity of firing. In the ventral tegmental area (VTA) low doses of (R)-8-OH-DPAT (2-32 micrograms/kg i.v.) caused an increase in all three parameters. The effect on firing rate of DA neurons was more pronounced in the parabrachial pigmentosus nucleus than in the paranigral nucleus, the two major subdivisions of VTA. In the substantia nigra zona compacta (SN-ZC), (R)-8-OH-DPAT (2-256 micrograms/kg i.v.) had no effect on firing rate and regularity of firing and only slightly increased burst firing. High doses of (R)-8-OH-DPAT (512-1024 micrograms/kg i.v.) decreased the activity of DA cells in both areas, an effect that was prevented by pretreatment with the selective DA D2 receptor antagonist raclopride. (S)-UH-301 (100-800 micrograms/kg i.v.) decreased both firing rate and burst firing without affecting regularity of DA neurons in the VTA. In the SN-ZC, (S)-UH-301 decreased the firing rate but failed to affect burst firing and regularity of firing. These effects of (S)-UH-301 were blocked by raclopride pretreatment. Local application by pneumatic ejection of 8-OH-DPAT excited the DA cells in both the VTA and the SN-ZC, whereas (S)-UH-301 inhibited these cells when given locally. These results show that 5-HT1A receptor related compounds differentially affect the electrophysiological activity of central DA neurons. The DA receptor agonistic properties of these compound appear to contribute to the inhibitory effects of high doses of (R)-8-OH-DPAT and (S)-UH-301 on DA neuronal activity. Given the potential use of 5-HT1A receptor selective compounds in the treatment of anxiety and depression their effects on central DA systems involved in mood regulation and reward related processes are of considerable importance.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Activation of brain noradrenergic neurons during recovery from halothane anesthesia. Persistence of phasic activation after clonidine.

BACKGROUND: alpha 2-Adrenoceptor agonists, known as antihypertensive agents, may be used during general anesthesia for their anesthetic sparing action and to reduce the occurrence of side effects. Previous studies have shown that the brain's noradrenergic nucleus, locus coeruleus, is an important target in mediating the hypnotic action of alpha 2 agonists. The authors studied the effects of recovery from halothane anesthesia on the electrical activity of locus coeruleus neurons to examine cellular substrates underlying the clinical effectiveness of alpha 2 agonists. METHODS: Experiments were performed in locally anesthetized rats, whose circulatory and acid-base stabilities were ensured by mechanical ventilation and volume infusion. Locus coeruleus neurons were recorded continuously while the rats were anesthetized with halothane (1%) and/or after the halothane was discontinued. RESULTS: Under the influence of halothane, locus coeruleus cells exhibited a slow, regular spontaneous discharge (1.95 +/- 0.23 Hz), and contralateral foot or tail pinch elicited a prominent, phasic activation in locus coeruleus neurons. Such phasic activation was blocked by local ejection of kynurenic acid, an excitatory amino acid antagonist, close to recorded neurons, but not by clonidine (up to 64 micrograms.kg-1). Thirty minutes after the halothane was discontinued, the mean firing rate of locus coeruleus neurons was increased by 87 +/- 20%. This excitation resulted from a prominent increase in bursting activity (21 +/- 5% of spikes in bursts vs. 4 +/- 1%) and was reversed by halothane readministration. This activation also was reduced by local ejection of kynurenic acid. Halothane discontinuance revealed the reactivity of locus coeruleus neurons to nonnoxious, sensory stimuli, and considerably reduced the apparent potency of intravenous administration of clonidine to inhibit locus coeruleus activity (effective dose for 50% of maximal effect (ED50), 25.48 +/- 8.26 micrograms.kg-1 vs. 4.81 +/- 0.80 micrograms.kg-1 under halothane). This decrease was caused by the persistence of bursting activity after the administration of clonidine, which was completely suppressed by readministration of halothane or local application of kynurenic acid. CONCLUSION: The data demonstrate: (1) that halothane withdrawal increases locus coeruleus neuronal activity via excitatory amino acid input, and this withdrawal-induced activity is characterized by a prominent burst (phasic) discharge; (2) that sedative doses of clonidine inhibit the tonic component of locus coeruleus activity but not the phasic activation of locus coeruleus neurons; and (3) that readministration of halothane or local ejection of an excitatory amino acid antagonist fully suppresses the bursting activity unaffected by clonidine.

Anesthesia Recovery Period↗
PubMed1992

Inhibition of locus coeruleus neurons by the phencyclidine analog, N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine: evidence for potent indirect adrenoceptor agonist properties.

The effects of the phencyclidine derivative, N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP), on the electrical activity of noradrenaline (NA) neurons of the locus coeruleus (LC) were studied in halothane-anesthetized rats. Systemic administration of BTCP potently inhibited LC neurons (ID50 of 1.1 +/- 0.1 mg/kg i.v.). This effect was mimicked by local microejection of BTCP into the LC. Both the systemic and local effects of BTCP were blocked by alpha 2-adrenoceptor antagonists and prevented by prior depletion of catecholamines with reserpine. These and other data suggest that BTCP behaves as a potent indirect NA agonist (i.e. via NA re-uptake and/or release systems).

Animals↗
PubMed1992

Combining in vivo volume-controlled pressure microejection with extracellular unit recording.

We report a method for combining extracellular single-unit recording with pressure ejection, permitting microvolume quantification through the measurement of meniscus movement. Good optimization of both high quality recording and precise determination (in the nanoliter range) of the pressure-ejected volume can be obtained by using a recording electrode affixed to a calibrated, narrow inner diameter ejection pipette.

Animals↗
PubMed1992

Relationship between dopamine release in the rat nucleus accumbens and the discharge activity of dopaminergic neurons during local in vivo application of amino acids in the ventral tegmental area.

Amino acids were pressure-ejected in the ventral tegmental area of rats which were anesthetized with chloral hydrate and treated with pargyline. The extracellular dopamine concentration was recorded from the nucleus accumbens with an electrochemically treated carbon fiber electrode combined either with differential normal pulse voltammetry or with differential pulse amperometry. In distinct rats the discharge activity of single dopaminergic neurons was monitored in the ventral tegmental area while amino acids were pressure-injected at a distance of 200-300 microns from the recorded cell. GABA (24 and 50 nl, 1 M) induced a complete and reversible inhibition of the firing rate lasting for 3-6 min and a decrease in the basal extracellular dopamine level (-54% and -66%, respectively). Glutamate (32 nl, 10 mM), N-methyl-D-aspartate and quisqualate (100 microM) stimulated the firing rate and enhanced the dopamine extracellular concentration up to 10-times the basal one (18 nM). These increases subsided within 1-5 min. Their amplitude depended on the ejected volume (from 16 to 65 nl). At the time-resolution of the method (some seconds) all these variations in the dopamine release appeared closely time-correlated with those of the firing rate. When the mean discharge rate is considered, N-methyl-D-aspartate was as potent as quisqualate but the former promoted burst firing while the latter induced a sustained activity. As regards dopamine release, N-methyl-D-aspartate was twice as potent as quisqualate. This further shows that dopaminergic terminals convert physiological impulse flow into dopamine release as a high pass filter which favors bursts of action potentials.

Animals↗
PubMed1992

Inhibition of nigral dopamine neurons by systemic and local apomorphine: possible contribution of dendritic autoreceptors.

Peripheral administration of low doses of dopamine agonist apomorphine induces a strong and short-latency inhibition of dopamine neurons in the substantia nigra, presumably via the activation of somatodendritic autoreceptors. We studied the site of action of apomorphine in anesthetized rats using volume-controlled pressure microejection combined with single unit recordings. Microapplication of apomorphine in the immediate vicinity of nigral dopamine neurons did not mimic the effect of intravenous administration of apomorphine (50 micrograms/kg), regardless of the concentration or volume used (10(-10)-10(-2) M, 10-100 nl). In contrast, the inhibition produced by systemic apomorphine was mimicked by drug application at a site 300 microns lateral and 600 microns ventral from the recording site in the zona reticulata of the substantia nigra, a region rich in dendrites of dopamine neurons. The inhibition induced by such a distant application of apomorphine could be reversed by systemic injection of D2, but not D1, receptor antagonists. Non-dopaminergic substances such as GABA, bicuculline or lidocaine were more effective when ejected close to rather than distant from the recording site, in a manner opposite to that of apomorphine. Similar to apomorphine, dopamine and D2 receptor agonists were more potent when intranigral applications were made at sites distant from, rather than close to, the recorded dopamine cells. Ejection of D2 antagonists in the substantia nigra zona reticulata attenuated the inhibitory effect of subsequent systemic apomorphine. Our results, together with other previous studies on the location of D2 receptors on dopamine neurons, suggest that peripheral administration of low doses of apomorphine inhibits nigral dopamine neurons by acting at D2 receptors located on the dendrites of these neurons.

Animals↗
PubMed1991

Anatomical and electrophysiological evidence for a glycinergic inhibitory innervation of the rat locus coeruleus.

Using a highly specific antiserum to glycine and a very sensitive immunohistochemical technique with streptavidin-horseradish peroxidase, we visualized for the first time a dense plexus of glycine varicose fibers in the locus ceruleus (LC) of the rat. We further demonstrated that iontophoretically applied glycine inhibits the spontaneous LC noradrenergic cell discharge and that this inhibition is blocked by co-iontophoresis of strychnine. These anatomical and electrophysiological results indicate that the rat locus ceruleus receives an inhibitory glycinergic input.

Animals↗
PubMed1991

Effect of modafinil and amphetamine on the rat catecholaminergic neuron activity.

We have studied the effect of modafinil and amphetamine, two waking drugs, on the electrical activity of central dopaminergic and noradrenergic neurons in the rat. Modafinil (128 mg/kg, i.p.) was unable to modify the firing pattern of these neurons, while amphetamine (2 or 5 mg/kg, i.p.) consistently inhibited their activity. A pretreatment with modafinil did not change thereafter the effect of amphetamine. Contrary to amphetamine, the waking effect of modafinil does not seem to be mediated by the catecholaminergic neuron activity per se.

Animals↗
PubMed1991

A method to maintain normal respiratory and metabolic state in artificially respired rats.

Analysis of arterial blood gases (ABG) in awake, paralyzed, locally anesthetized, and artificially respired rats revealed the development with time of severe hypoxemia associated with metabolic acidosis despite adequate ventilation as assessed by normal PaCO2. These respiratory and metabolic disturbances may underlie the progressive deterioration experienced with this preparation frequently used in neuropharmacological experiments. We report here that the intravascular infusion of bicarbonated artificial plasma, associated with continuous positive pressure ventilation, prevents the deterioration of the respiratory and metabolic state in this preparation, which can be maintained within the range of that of the freely moving animal. This stabilized preparation may thus be highly suitable for neuropharmacological experiments extending for several hours.

Anesthesia↗
PubMed1991

Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology.

Tract-tracing and electrophysiology studies have revealed that major inputs to the nucleus locus coeruleus (LC) are found in two structures, the nucleus paragigantocellularis (PGi) and the perifascicular area of the nucleus prepositus hypoglossi (PrH), both located in the rostral medulla. Minor afferents to LC were found in the dorsal cap of the paraventricular hypothalamus and spinal lamina X. Recent studies have also revealed limited inputs from two areas nearby the LC, the caudal midbrain periaqueductal gray (PAG) and the ventromedial pericoerulear region. The pericoeruleus may provide a local circuit interface to LC neurons. Recent electron microscopic analyses have revealed that LC dendrites extend preferentially into the rostromedial and caudal juxtaependymal pericoerulear regions. These extracoerulear LC dendrites may receive afferents in addition to those projecting to LC proper. However, single-pulse stimulation of inputs to such dendritic regions reveals little or no effect on LC neurons. Double-labeling studies have revealed that a variety of neurotransmitters impinging on LC neurons originate in its two major afferents, PGi and PrH. The LC is innervated by PGi neurons that stain for markers of adrenalin, enkephalin or corticotropin-releasing factor. Within PrH, large proportions of LC-projecting neurons stained for GABA or met-enkephalin. Finally, in contrast to previous conclusions, the dorsal raphe does not provide the robust 5-HT innervation found in the LC. We conclude that 5-HT inputs may derive from local 5-HT neurons in the pericoerulear area. Neuropharmacology experiments revealed that the PGi provides a potent excitatory amino acid (EAA) input to the LC, acting primarily at non-NMDA receptors in the LC. Other studies indicated that this pathway mediates certain sensory responses of LC neurons. NMDA-mediated sensory responses were also revealed during local infusion of magnesium-free solutions. Finally, adrenergic inhibition of LC from PGi could also be detected in nearly every LC neuron tested when the EAA-mediated excitation is first eliminated. In contrast to PGi, the PrH potently and consistently inhibited LC neurons via a GABAergic projection acting at GABAA receptors within LC. Such PrH stimulation also potently attenuated LC sensory responses. Finally, afferents to PGi areas that also contain LC-projecting neurons were identified. Major inputs were primarily autonomic in nature, and included the caudal medullary reticular formation, the parabrachial and Kölliker-Fuse nuclei, the PAG, NTS and certain hypothalamic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1991

Burst firing of mesencephalic dopamine neurons is inhibited by somatodendritic application of kynurenate.

Midbrain dopamine neurons of the zona compacta substantia nigra (SN) and ventral tegmental area (VTA), giving rise to the nigrostriatal and mesolimbocortical midbrain dopamine pathways, respectively, typically display a spontaneous activity consisting of single spikes and bursts. Previously, intracerebroventricular administration of the excitatory amino acid (EAA) antagonist kynurenate has been shown to inhibit burst firing and induce a regular, pacemaker-like firing of ventral tegmental area midbrain dopamine neurons. In the present experiments, zona compacta substantia nigra and ventral tegmental area midbrain dopamine neurons were recorded in the chloral hydrate anaesthetized male rat. Kynurenate was administered locally, either by micro-iontophoresis or by pneumatic (micropressure) ejection. Both forms of local kynurenate application produced an immediate inhibition of burst firing and a slightly increased regularity of firing in both zona compacta substantia nigra and ventral tegmental area midbrain dopamine neurons. The present results indicate that excitatory amino acid nerves tonically modulate midbrain dopamine neuronal burst firing directly on the midbrain dopamine cell bodies, further stressing the importance of excitatory amino acid innervation in the physiological function of midbrain dopamine neurons, particularly in the dynamic aspects involved in the behavioural modulation and pharmacological responses of these psychopharmacologically important neurons.

Action Potentials↗
PubMed1991

Serotonin selectively attenuates glutamate-evoked activation of noradrenergic locus coeruleus neurons.

The effect of 5-HT on activity of noradrenergic locus coeruleus (LC) neurons was studied using microiontophoretic and micropressure drug application in anesthetized rats. 5-HT had no consistent effect on LC spontaneous discharge, eliciting a modest decrease overall. However, 5-HT reliably attenuated responses of LC neurons to excitatory amino acids (EAAs), one of the major classes of transmitters in afferents to these neurons. This effect was specific for EAA responses because it occurred for glutamate and kainate but not for ACh. In contrast, iontophoretic norepinephrine (NE) selectively attenuated spontaneous activity but not responses evoked by either glutamate or ACh. The responsiveness of LC neurons to EAAs as quantified by a response-contrast measure (evoked excitation/basal activity) was markedly reduced by 5-HT, but was increased by NE. For ACh, such responsiveness of LC cells was not changed by 5-HT, but was increased by NE. The effects of 5-HT were prevented and reversed by iontophoretically applied antagonists of 5-HT receptors, methysergide and methiothepin. Thus, 5-HT appears to selectively interact with EAA responses of LC neurons, acting as a filter to attenuate LC activity linked to its major EAA inputs while allowing other channels afferent to the LC (e.g., those utilizing ACh) to be expressed.

Acetylcholine↗
PubMed1991

[Participation of NMDA receptors in spontaneous burst firing of dopaminergic mesencephalic neurons].

In the rat, somatodendritic application of the NMDA antagonist AP-5, within the Substantia Nigra Zona Compacta and Ventral Tegmental Area, either by micro-iontophoresis or pressure ejection, reduces burst firing of dopamine neurons. Similar local application of the non-NMDA antagonist CNQX does not affect their firing pattern. These results indicate that, in vivo, excitatory amino acid afferents participate through NMDA receptors in the control of the spontaneous burst firing of midbrain dopamine neurons.

Action Potentials↗
PubMed1991

[Participation of 5-HT 1A receptors in the decrease by serotonin of activation of locus coeruleus neurons by glutamate].

The serotonin-induced decrease of glutamate-evoked activation of noradrenergic locus coeruleus neurons is mimicked by agonists of 5-HT 1 and 1A but not by 5-HT 1B or by 5-HT 2 agonists. Moreover, this effect is reversed by a broad-spectrum 5-HT antagonist but not by a 5-HT 2 antagonist, indicating that this effect is mediated primarily through 5-HT 1A receptors.

Animals↗
PubMed1990

The effect of acetylcholine on rat olfactory bulb unit activity.

The olfactory bulb (OB) of the rat receives an extrinsic innervation from the most anterior part of the basal forebrain cholinergic complex. The effect of microiontophoretically applied acetylcholine (ACh) on OB unit activity was studied in 16 adult male rats. A total of 80 units was recorded and in 50% of the cases the cell layer where the recording was done was clearly identified. The results provide evidence for a particularly high level of sensitivity to ACh in the outer glomerular layer (73%). Both inhibitory and excitatory responses were found. These results are in agreement with histological studies indicating that this layer presents the highest density of cholinergic terminals. As a whole, present knowledge suggests the existence of a strong cholinergic control of the olfactory input at the level of the first synapse in the system.

Acetylcholine↗
PubMed1989

Apomorphine-induced inhibition of substantia nigra dopamine neurons: effects of unilateral injection through the internal carotid artery.

Possible indirect components in the inhibition of firing of A9 dopamine neurons induced by systemic apomorphine were studied using unilateral drug administration through the internal carotid artery, known to irrigate only the ipsilateral mid- and forebrain. When compared to intravenous injection, unilateral intracarotid administration inhibited ipsilateral neurons with a marked decrease of both the latency (less than 1 s) and the dose required for complete inhibition, whereas contralateral neurons were not affected. This suggests a first-pass central effect of apomorphine, presumably associated with brain extraction. Thus, peripheral and hindbrain targets do not seem to contribute to the inhibitory effect of low doses of systemic apomorphine. An intranigral possible mode of action is discussed in view of the particular arrangement of dopaminergic dendrites within the zona reticulata.

Action Potentials↗