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C de Montigny

Publications and source records attributed to C de Montigny.

At least 127 records · Page 7Linked to original sources
PubMed1987

Diurnal rhythms in the responsiveness of hippocampal pyramidal neurons to serotonin, norepinephrine, gamma-aminobutyric acid and acetylcholine.

Radioligand binding studies have revealed the existence of endogenous circadian rhythms in the number of several receptors in the rat brain. The present microiontophoretic study was undertaken to assess diurnal rhythms in the responsiveness of rat hippocampal pyramidal neurons to serotonin (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA), and acetylcholine (ACh). Between December and April, there was a significant diurnal variation in the responsiveness of hippocampal pyramidal neurons to 5-HT and ACh. Between May and August, the responsiveness to NE and ACh showed a diurnal variation. There was no diurnal variation in the responsiveness to GABA in either period of the year. Short-term exposure to constant light or darkness produced a phase-shift of the serotoninergic and cholinergic rhythms, suggesting their endogenous nature and their synchronization to clock-time by the light-dark cycle. The diurnal rhythms in responsiveness to 5-HT and NE underwent phase-shifts from the December-April to the May-August period in rats entrained to 12:12 light-dark cycle, suggesting the existence of seasonal modulation of these rhythms. These circadian rhythms in the postsynaptic responsiveness of hippocampal pyramidal cells and their seasonal fluctuation may be related to the diurnal variation of mood seen in major depression as well as to the seasonal incidence of this illness.

Acetylcholine↗
PubMed1987

A comparative double-blind controlled study of trimipramine and amitriptyline in major depression: lack of correlation with 5-hydroxytryptamine reuptake blockade.

Thirty-four hospitalized patients with major depression were enrolled in a 3-week double-blind parallel comparative study of trimipramine and amitriptyline. Following a 1-week washout period, patients randomly received one of the two drugs up to 100 mg twice daily on a fixed increment dosage schedule. Both treatments produced a rapid significant clinical improvement that occurred in a predominantly linear fashion. The pattern of improvement was very similar with both drugs. There was no significant correlation between plasma levels of trimipramine and desmethyl-trimipramine and clinical improvement. A negative correlation between amitriptyline plasma levels and clinical improvement was found, whereas a positive correlation occurred with the nortriptyline levels. Amitriptyline, and to a lesser extent trimipramine, prolonged intracardiac conduction. In the amitriptyline group only, this effect was accompanied by significant increases of heart rate and blood pressure. Platelet serotonin content was decreased by 57% by the amitriptyline treatment but remained unchanged in the trimipramine group. This finding constitutes the first clinical evidence that trimipramine does not exert its antidepressant effect through 5-hydroxytryptamine reuptake blockade. It is proposed that neuronal sensitization to 5-hydroxytryptamine might mediate the therapeutic effect of tricyclic antidepressant drugs.

Adult↗
PubMed1987

Modifications of the serotonin system by antidepressant treatments: implications for the therapeutic response in major depression.

Results of electrophysiological single-cell recording studies suggest that most, if not all, types of antidepressant treatments increase 5-hydroxytryptamine (5-HT) neurotransmission. Tricyclic antidepressants, electroconvulsive shock treatment, mianserin, adinazolam, and possibly sleep deprivation may exert their therapeutic effect through sensitization of postsynaptic neurons to 5-HT. Serotonin reuptake blockers may relieve depression through an increased efficacy of the presynaptic element resulting from a desensitization of somatodendritic and terminal 5-HT autoreceptors. Similarly, monoamine oxidase inhibitors may act by increasing the efficacy of 5-HT neurons. Intensification of 5-HT function appears to be a common denominator to antidepressant treatments; however, evidence suggests that this modification may only be a link in a chain of events leading to an antidepressant response.

Animals↗
PubMed1986

Effects of a selective 5-HT reuptake blocker, citalopram, on the sensitivity of 5-HT autoreceptors: electrophysiological studies in the rat brain.

Citalopram (CIT), is a selective serotonin (5-HT) reuptake blocker and a clinically effective antidepressant. The present electrophysiological studies were undertaken to investigate in vivo the acute and long-term effects of CIT administration on 5-HT neurotransmission. In a first series of experiments, a single dose of CIT (0.05-0.5 mg/kg) was administered intravenously to naive rats while recording the activity of a 5-HT-containing neuron in the nucleus raphe dorsalis. A dose-response relationship of the inhibitory effect of CIT on the firing activity of 5-HT neurons was obtained with an ED50 of 0.23 +/- 0.03 mg/kg. In a second series of experiments, rats were treated with CIT (20 mg/kg/day, i.p.) for 2, 7 and 14 days. In rats treated for 2 days, there was a marked reduction in the firing activity of 5-HT neurons in the nucleus raphe dorsalis; there was a partial recovery after 7 days and a complete recovery after 14 days of treatment. The response of 5-HT neurons to intravenously administered LSD was decreased in rats treated for 14 days with CIT, indicating a desensitization of the somatodendritic 5-HT autoreceptor. In a third series of experiments, carried out in rats treated with CIT (20 mg/kg/day, i.p.) for 14 days, the suppression of firing activity of CA3 hippocampal pyramidal neurons produced by microiontophoretically-applied 5-HT and by the electrical activation of the ascending 5-HT pathway was measured. Long-term treatment with CIT did not modify the responsiveness of these neurons to microiontophoretically-applied 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of repeated amiflamine administration on serotonergic and noradrenergic neurotransmission: electrophysiological studies in the rat CNS.

Amiflamine is a selective and reversible inhibitor of monoamine oxidase (MAO) type A which exerts a preferential effect on serotonin (5-HT) catabolism. The present studies were undertaken to compare the effects of repeated administration of amiflamine (2 mg/kg, twice daily) on several aspects of the functioning of the 5-HT and norepinephrine (NE) systems in the rat CNS. The activity of MAO-A and B was assessed in forebrain slices and the whole brain contents of the neurotransmitters and their metabolites were determined by HPLC after 2-, 7- and 21-day treatments. MAO-A was inhibited by about 50% 2 h after the last dose and its activity was back to normal in rats sacrificed 12 h after the last dose. The activity of MAO-B was unaffected two or 12 h after the last dose. Whole brain concentration of 5-HT was increased to a greater degree than that of NE following repeated administration of amiflamine. These increases in 5-HT and NE were accompanied by decreased levels of their respective metabolites 5-hydroxy-indoleacetic acid and 3-methoxy-4-hydroxyphenylethyleneglycol. The firing activity of dorsal raphe 5-HT neurons, but not that of NE neurons, was markedly decreased 2-6 h after the last dose of a 2-day treatment. However, 2-6 h after a 21-day treatment, the firing activity of 5-HT neurons was back to normal, whereas that of NE neurons was decreased by 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1986

In vivo electrophysiological evidence for the regulatory role of autoreceptors on serotonergic terminals.

The present in vivo studies were undertaken to evaluate electrophysiologically the modulatory role of the terminal 5-HT autoreceptor on 5-HT neurotransmission. In a first series of experiments, the effect of the electrical activation of the ascending 5-HT pathway on the firing activity of CA3 hippocampal pyramidal neurons was measured before and after the intravenous administration of methiothepin, a terminal 5-HT autoreceptor antagonist. Methiothepin significantly increased the duration of the suppression of firing activity of these neurons by the electrical stimulation of the 5-HT pathway, without modifying their responsiveness to microiontophoretically applied 5-HT. This suggests that endogenously released 5-HT activates the 5-HT terminal autoreceptor and that methiothepin enhances the efficacy of 5-HT synaptic transmission by blocking this activation. In a second series of experiments, further evidence for the activation of terminal 5-HT autoreceptors by 5-HT released by the electrical stimulation was sought by assessing the effectiveness of 2 series of stimulations of the ascending 5-HT pathway delivered at different frequencies while recording the same postsynaptic neuron. Increasing the frequency of stimulation (from 0.8 to 5 Hz) significantly reduced the duration of suppression of firing activity of the postsynaptic neurons. This difference between the 0.8 and 5 Hz stimulations was decreased by intravenous methiothepin, suggesting that the reduced effectiveness of the stimulations delivered at the higher frequency is attributable to a greater activation of the terminal 5-HT autoreceptor. These results provide direct electrophysiological evidence for the modulatory role of the 5-HT terminal autoreceptor on 5-HT neurotransmission.

Animals↗
PubMed1985

High incidence of multisystemic reactions to zimeldine.

Forty-five patients suffering from a major depression were administered zimeldine, amitriptyline or placebo (15 patients in each group) in a double-blind controlled study. In the zimeldine group, seven of the 14 patients treated for more than one week presented a toxic syndrome consisting in a severe prostration, fever, myalgias and arthralgias. In all patients presenting this syndrome, laboratory analyses revealed an elevation of alkaline phosphatase and of aspartate and alanine aminotransferases and a decrease in white blood cell and platelet counts. Three patients presented a mild proteinuria and hematuria. Although an immunological mechanism cannot be ruled out, several characteristics of this reaction suggest the formation of a metabolite of zimeldine with direct cellular toxicity. The relatively high starting dose of 200 mg/day of zimeldine administered in the present study and the increment to 300 mg/day after only seven days might have contributed to the high incidence of toxic reactions observed.

Adult↗
PubMed1985

Serotoninergic but not noradrenergic neurons in rat central nervous system adapt to long-term treatment with monoamine oxidase inhibitors.

Repeated administration of monoamine oxidase inhibitors induces a transient decrease in the firing rate of serotoninergic neurons followed by complete recovery, whereas it results in a persistent reduction of the firing rate of noradrenergic neurons. Under these conditions, serotoninergic, but not noradrenergic, neurons undergo a desensitization of their somatic autoreceptors. Serotoninergic neurons therefore show the capacity to free themselves from their autoregulatory control, a property which noradrenergic neurons appear to be lacking. The time course of the recovery in the firing rate of the serotoninergic neurons is consistent with the delayed antidepressant effect of monoamine oxidase inhibitors.

Animals↗
PubMed1985

Rapid response to the addition of lithium in iprindole-resistant unipolar depression: a pilot study.

The authors administered lithium carbonate, 900 mg/day, in an open study to seven patients with a major unipolar depression refractory to 3-week treatment with iprindole, 90 mg/day, a tricyclic antidepressant devoid of any action on monoaminergic reuptake. All patients showed clinically significant improvement within 48 hours. Since iprindole induces in the animal a sensitization of forebrain neurons to serotonin (5-HT), as do other tricyclic antidepressants, and lithium enhances the activity of 5-HT neurons, the authors propose that an enhanced release of 5-HT on sensitized target neurons might underlie the rapid antidepressant effect in tricyclic-refractory depression when lithium is added to the treatment regimen.

Adult↗
PubMed1984

Effects of the two antidepressant drugs mianserin and indalpine on the serotonergic system: single-cell studies in the rat.

Several antidepressant treatments enhance serotonergic neurotransmission. The present electrophysiological studies were undertaken to assess the effect of mianserin and indalpine, two antidepressant drugs with different pharmacological profiles, on serotonergic neurotransmission. In a first series of experiments, the responsiveness of hippocampal pyramidal neurons to microiontophoretic applications of serotonin (5-HT), norepinephrine (NE) and gamma-aminobutyric acid (GABA) was assessed following mianserin, imipramine (5 mg/kg/day IP) or saline administration for 14 days. At 48 h after the last dose of mianserin, responsiveness to 5-HT was increased whereas that to NE and GABA was not modified. The degree of sensitization to 5-HT was the same as that produced by imipramine. Acute IV administration of mianserin (up to 10 mg/kg) did not decrease the firing rate of dorsal raphe 5-HT neurons. In a second series of experiments, long-term administration of indalpine (5 mg/kg/day IP for 14 days) did not modify the responsiveness of hippocampal pyramidal neurons to microiontophoretically applied 5-HT, NE and GABA whereas imipramine treatment (5 mg/kg/day IP) increased selectively their sensitivity to 5-HT when compared to indalpine-treated rats. In keeping with its potent reuptake-blocking property, acute IV indalpine produced a marked decrease in the firing rate of dorsal raphe 5-HT neurons (ED50 0.33 mg/kg). The firing rate of dorsal raphe 5-HT neurons was assessed following 2-, 7- and 14-day treatments with indalpine (5 mg/day IP). After 2 days, the firing rate of 5-HT neurons was greatly reduced, after 7 days it had recovered partially and after 14 days it had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1984

Electroconvulsive shock treatments enhance responsiveness of forebrain neurons to serotonin.

Electroconvulsive therapy remains one of the most effective treatments of major depression. The effect of electroconvulsive shocks (ECSs) on the responsiveness of hippocampal pyramidal neurons to serotonin, norepinephrine, gamma-aminobutyric acid and 5-methoxydimethyltryptamine was studied in rats pretreated with one or six ECSs. Control rats were given subconvulsive shocks. Microiontophoretic experiments were conducted 36 hr after the last shock in urethane-anesthetized or low cerveau isolé preparations. Responsiveness of hippocampal pyramidal neurons to microiontophoretic applications of serotonin was markedly enhanced in rats pretreated with six ECSs. Responsiveness to 5-methoxydimethyltryptamine, a postsynaptic agonist which is not an adequate substrate for the high-affinity serotonin reuptake process, was also enhanced in rats pretreated with six ECSs, indicating that the increased responsiveness to serotonin was due to a postsynaptic modification. The effects of norepinephrine and of gamma-aminobutyric acid applied on the same neurons were not modified by repeated ECS pretreatment. A single ECS failed to modify responsiveness to either serotonin or 5-methoxydimethyltryptamine. Inasmuch as long-term tricyclic antidepressant drug administration has been shown to produce a similar sensitization to serotonin, the present results suggest that enhancement of serotonergic neurotransmission might mediate the therapeutic effect of both types of treatment in major depression.

Animals↗
PubMed1983

Lithium carbonate addition in tricyclic antidepressant-resistant unipolar depression. Correlations with the neurobiologic actions of tricyclic antidepressant drugs and lithium ion on the serotonin system.

Preliminary reports suggested that the addition of lithium carbonate to the regimen of patients treated with, but not responding to, a tricyclic antidepressant (TCA) drug can induce a rapid alleviation of depression. We examined the effect of lithium carbonate addition in 39 patients with unipolar depression whose conditions were not improved by at least three weeks' TCA drug administration. In 30 of 42 observations, lithium carbonate brought about a greater than 50% improvement within 48 hours. In a second study, the effects of lithium carbonate addition were compared in five amitriptyline hydrochloride-pretreated and five placebo-pretreated patients who showed no improvement after a three-week treatment. All five patients receiving amitriptyline showed a greater than 50% improvement 48 hours after lithium carbonate addition, whereas only one patient in the placebo group showed a marked response. In a third study the effect of lithium carbonate withdrawal was studied in nine TCA-resistant patients who had shown a marked improvement 48 hours after lithium addition. Only five of these patients had a relapse five days after lithium discontinuation. Since animal studies have shown that TCA drugs sensitize forebrain neurons to serotonin and that lithium enhances the activity of serotonin-containing neurons, we propose that the antidepressant effect of lithium addition in TCA-resistant patients might be mediated by enhancing serotonin neurotransmission.

Adult↗
PubMed1983

Effects of quipazine on pre- and postsynaptic serotonin receptors: single cell studies in the rat CNS.

Many behavioural and biochemical studies have pointed to an agonistic activity of quipazine on serotonin (5-HT) receptors. In the present electrophysiological study, the effect of quipazine on pre- and postsynaptic 5-HT receptors in the rat was studied. Quipazine, administered intravenously, depressed the firing rate of 5-HT-containing dorsal raphe neurones (ED50 = 0.82 mg/kg). Microiontophoretic applications of quipazine on 5-HT-containing neurones in the dorsal raphe and on neurones of two forebrain regions receiving a 5-HT input (the ventral lateral geniculate nucleus and the dorsal hippocampus) consistently depressed neuronal firing rate as did 5-HT and D-lysergic acid diethylamide (LSD). Quipazine was more potent on 5-HT neurones than on the ventral lateral geniculate nucleus and hippocampal neurones: the post/presynaptic efficacy ratio for quipazine was similar to that of LSD. Following a selective denervation of 5-HT neurones with intraventricular injection of 5,7-di-hydroxy-tryptamine in desipramine-pretreated rats, the responsiveness of neurones in the ventral lateral geniculate nucleus to quipazine, applied microiontophoretically, was increased as was that to 5-HT and to LSD. These results provide direct evidence for the agonistic activity of quipazine on both pre- and postsynaptic 5-HT receptors.

Animals↗