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C de Montigny

Publications and source records attributed to C de Montigny.

At least 91 records · Page 5Linked to original sources
PubMed1991

Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--I. Effects of acute and long-term administration of tandospirone on serotonin neurotransmission.

The acute and long-term effects of the antidepressant/anxiolytic selective 5-HT1A receptor ligand, tandospirone (SM-3997) on 5-HT neurotransmission were assessed using single-cell extracellular recording in chloral hydrate-anaesthetized rats. The acute intravenous administration of tandospirone decreased the firing rate of 5-HT neurones of the dorsal raphe (ED50 = 9.1 +/- 1.1 micrograms/kg). A treatment with tandospirone for 2 days (10 mg/kg/day, s.c.), markedly reduced the firing activity of 5-HT neurones of the dorsal raphe; this was followed by a partial recovery after 7 days and by complete recovery after 14 days of administration of tandospirone. After treatment with tandospirone for 14 days (10 mg/kg/day, s.c.), the responsiveness of 5-HT neurones to the intravenous administration of LSD was reduced, suggesting that somatodendritic 5-HT autoreceptors had desensitized. The depressant effects of microiontophoretically-applied tandospirone and 5-HT, on the firing activity of CA3 pyramidal neurones in the hippocampus were blocked by the intravenous injection of the 5-HT1A receptor antagonist, BMY-7378. The depressant effect of microiontophoretically-applied 5-HT onto these same neurones was markedly reduced during concurrent background application of tandospirone, suggesting that the latter acted as a partial agonist at postsynaptic 5-HT1A receptors. The sustained administration of tandospirone for 14 days (10 mg/kg/day, s.c.) altered neither the effectiveness of microiontophoretically-applied 5-HT and tandospirone nor that of endogenous 5-HT, released by the electrical simulation of the afferent 5-HT pathway, in suppressing the firing activity of pyramidal neurones in the hippocampus, suggesting that postsynaptic 5-HT1A receptors had not desensitized. Furthermore, long-term treatment with tandospirone did not alter the sensitivity of the terminal 5-HT autoreceptor. It is thus concluded that desensitization of somatodendritic 5-HT autoreceptors permits 5-HT neurones to regain their physiological rate of firing during long-term treatment with tandospirone and, consequently, to release a normal amount of 5-HT into the synaptic cleft. This, combined with the sustained activation of normosensitive postsynaptic 5-HT1A receptors by tandospirone, during such a treatment, should result in an enhanced tonic activation of postsynaptic 5-HT1A receptors.

Animals↗
PubMed1991

Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--II. Effects of acute administration of 1-PP and long-term administration of tandospirone on noradrenergic neurotransmission.

1-(2-Pyrimidinyl)-piperazine (1-PP) is a common metabolite of the antidepressant/anxiolytic 5-HT1A agonists, tandospirone (SM-3997), gepirone, buspirone and ipsapirone. The present electrophysiological studies were undertaken to characterize in vivo the effect of 1-PP on noradrenergic (NE) neurotransmission in rat brain. At small doses, 1-PP (ED50 = 80 micrograms/kg, i.v.) reversed the depressant effect of the alpha 2-adrenoceptor agonist, clonidine (20 micrograms/kg, i.v.) on the firing activity of NE neurones of the locus coeruleus. After long-term treatment with tandospirone (10 mg/kg/day, s.c. x 14 days), the responsiveness of these NE neurones to intravenous administration of clonidine was decreased but their mean firing frequency remained within the control range. The effect of 1-PP on the postsynaptic alpha 2-adrenoceptor of pyramidal neurones in the hippocampus was investigated: intravenous administration of 1-PP (2-8 mg/kg, i.v.) reduced the effect of microiontophoretically-applied NE on CA3 pyramidal neurones of the dorsal hippocampus, without affecting their responsiveness to GABA and 5-HT. The effect of the electrical stimulation of NE neurones of the locus coeruleus in reducing firing activity of pyramidal neurones, which is mediated by postsynaptic alpha 1-adrenoceptors, was increased by 47% after acute administration of 1-PP (4 mg/kg, i.v.), presumably as a result of blockade of terminal alpha 2-autoreceptors. The effectiveness of these stimulations remained unchanged after long-term treatment with tandospirone. Furthermore, the decrease in the effectiveness of stimulation of the locus coeruleus, obtained by increasing the frequency from 1 to 5 Hz, a phenomenon due to an increased activation of terminal alpha 2-adrenergic autoreceptors by endogenous NE, remained unaltered after long-term treatment with tandospirone. In addition to the initial depressant effect, stimulation of the locus coeruleus induces a late activation of these neurones which is mediated by a beta-adrenoceptor. The degree of activation induced by stimulation of the locus coeruleus was similar in controls and in long-term tandospirone-treated rats. It is concluded that 1-PP acts as an antagonist at somatodendritic and terminal alpha 2-adrenergic autoreceptors, as well as at postsynaptic alpha 2-adrenoceptors, in the central nervous system of the rat. However, the levels of 1-PP attained after long-term administration of tandospirone were not sufficient to modify NE neurotransmission.

Animals↗
PubMed1991

Effects of long-term desipramine administration on noradrenergic neurotransmission: electrophysiological studies in the rat brain.

The present studies were undertaken to assess in vivo the effects of repeated administration of the norepinephrine (NE) reuptake blocker desipramine (DMI) (5 or 10 mg/kg/day x 14 days) on five subsets of adrenoceptors and on the effectiveness of the NE reuptake process in the rat central nervous system. These receptors were: 1) the postsynaptic alpha-2 adrenoceptors which signal the suppressant effect of microiontophoretically applied NE on the firing activity of dorsal hippocampus pyramidal neurons; 2) the postsynaptic alpha-1 adrenoceptors which mediate the short-latency suppressant effect of endogenous NE, released by the electrical stimulation of the locus ceruleus (LC), on the firing activity of these same neurons; 3) the postsynaptic beta adrenoceptors which mediate the long-latency excitatory effect of LC stimulation on hippocampus pyramidal neurons; 4) the alpha-2 autoreceptors located on NE terminals in the hippocampus; and 5) the alpha-2 autoreceptors located on the cell body of LC NE neurons. The suppressant effect of microiontophoretic applications of NE on dorsal hippocampus pyramidal neurons was not changed by the long-term DMI treatments. The recovery time of the firing activity of these neurons after microiontophoretic application of NE, an index of the activity of the NE reuptake process, was the same in control and DMI-treated rats. However, the prolongation of this recovery time by the acute i.v. administration of DMI reached a plateau at a lower cumulative dose in long-term DMI-treated than in control rats. These results thus suggest that long-term administration of DMI did not affect the function of the NE transporter but reduced the number of DMI binding sites. The effectiveness of the 1 Hz stimulation of the LC in suppressing of the firing activity of pyramidal neurons was unchanged by either long-term DMI treatment (5 or 10 mg/kg/day), whereas that of the 5 Hz stimulation was enhanced only in rats on the 10-mg/kg regimen. This suggests that the function of terminal alpha-2 autoreceptors was decreased after this latter DMI regimen, because the reduction of the efficacy of the stimulation obtained by increasing the frequency from 1 to 5 Hz has been shown to be due to the activation of terminal alpha-2 adrenergic autoreceptors. In keeping with this interpretation, the reduction of the effectiveness of the stimulation of the LC by the systemic administration of the alpha-2 adrenoceptor agonist clonidine was attenuated in rats treated with the 10-mg/kg/day regimen of DMI, but not in those with the 5-mg/kg/day regimen.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Presynaptic and postsynaptic modifications of the serotonin system by long-term administration of antidepressant treatments. An in vivo electrophysiologic study in the rat.

The neurobiologic mechanisms whereby the long-term administration of different antidepressant treatments enhance the efficacy of 5-HT synaptic transmission was investigated using an electrophysiologic paradigm in chloral hydrate anesthetized rats. Repeated electroconvulsive shocks (ECS; administered every other day for 14 days) as well as the sustained 21-day administration of the tricyclic antidepressant imipramine (10 mg/kg/day) and of the selective 5-hydroxytryptamine (5-HT) reuptake blocker paroxetine (5 mg/kg/day), increased the suppressant effect of the electrical stimulation of the afferent 5-HT pathway on the firing activity of CA3 hippocampus pyramidal neurons. The long-term treatments with imipramine and ECS, but not with paroxetine, increased the responsiveness of postsynaptic CA3 hippocampus pyramidal neurons to the microiontophoretic application of 5-HT and to that of the selective 5-HT1A receptor ligand 8-OH-DPAT. In contrast, the long-term treatment with paroxetine, but not with imipramine or ECS, attenuated the negative feedback exerted by terminal 5-HT autoreceptors on 5-HT release. This was indicated by two series of experiments. First, the capacity of the acute intravenous injection of the terminal 5-HT autoreceptor antagonist methiothepin to increase the efficacy of the stimulation was abolished in paroxetine-treated rats. Second, the decreased suppressant effect on pyramidal neuron firing activity usually obtained by increasing the frequency of the stimulation from 1 to 5 Hz (shown to be due to an increase in terminal 5-HT autoreceptor activation at the higher frequency) was also reduced in paroxetine-treated rats. The present data confirm and extend those of previous electrophysiologic studies showing that an enhanced 5-HT synaptic transmission is a common end result of long-term administration of various types of antidepressant treatments. Furthermore, they suggest that the mechanisms underlying this enhanced synaptic transmission differ according to the type of treatment administered. Tricyclic antidepressants and ECS enhance 5-HT synaptic transmission by increasing the sensitivity of postsynaptic 5-HT1A receptors, whereas selective 5-HT reuptake blockers produce this effect by reducing the function of terminal 5-HT autoreceptors, thereby increasing the amount of 5-HT released per stimulation-triggered action potential.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Characterization of 5-HT1D receptor binding sites in post-mortem human brain cortex.

The present study provides further evidence for the presence of serotonin1D (5-HT1D) receptors in post-mortem human brain. Receptor binding parameters in temporal cortex homogenates were assessed using [3H]5-HT in the presence of 100 nM 8-OH-DPAT, 1 microM propranolol and 1 microM mesulergine to prevent labelling of the 5-HT1A, 5-HT1B and 5-HT1C sites, respectively. Under these conditions, [3H]5-HT apparently bound to a class of high affinity (Kd = 5.0 +/- 1.0 nM) low capacity (Bmax = 96 +/- 23 fmol/mg protein) sites. In competition experiments, 5-HT and 5-carboxyamidotryptamine (5-CT), as well as ergotamine, lysergic acid, sumatriptan and RU-24969 exhibited high affinity for these sites. This pharmacological profile is concordant with the ligand selectivity pattern reported for 5-HT1D receptors in other species and thus provides further evidence for its existence in human temporal cortex. In addition, the competition profile of some ligands, particularly of unlabelled 5-HT, 5-CT and ergotamine, revealed the existence of a lower affinity binding site. The latter suggests receptor heterogeneity or the presence of a lower affinity state of 5-HT1D receptors.

Adolescent↗
PubMed1990

Benzodiazepine receptors modulating serotonergic neurotransmission in rat hippocampus do not desensitize after long-term diazepam treatment.

Previous studies have shown in the rat that long-term diazepam treatment induces a desensitization of gamma-aminobutyric acid (GABA) benzodiazepine receptors which modulate serotonergic (5-HT) neuron firing activity in the dorsal raphe. We have examined the effect of a 21-day treatment with diazepam (5 mg/kg/day, i.p.) on the benzodiazepine receptors (BZR) which modulate the efficacy of the electrical stimulation of the ascending 5-HT pathway in suppressing the firing activity of rat dorsal hippocampus pyramidal neurons. The efficacy of the stimulation was not modified 24 h after the last dose of diazepam. Moreover, the potentiating effect of acute diazepam (1 mg/kg, i.v.) on the efficacy of the stimulation was similar in diazepam- and vehicle-treated rats. These results indicate that GABA-benzodiazepine receptors that modulate the release of 5-HT in the rat dorsal hippocampus are not desensitized by long-term diazepam treatment.

Animals↗
PubMed1990

Effects of short-term serotonin depletion on the efficacy of serotonin neurotransmission: electrophysiological studies in the rat central nervous system.

The effects of short-term serotonin (5-HT) depletion by p-chlorophenylalanine (PCPA) on the firing activity of dorsal raphe nucleus 5-HT neurons, on the responsiveness of dorsal hippocampus pyramidal neurons to microiontophoretically applied 5-HT and on the efficacy of the electrical stimulation of the ascending 5-HT pathway in suppressing the firing activity of CA3 dorsal hippocampus pyramidal neurons were assessed in chloral hydrate-anesthetized rats. PCPA (250 mg/kg/day i.p. for 2 days) reduced the 5-HT content of the dorsal hippocampus by 90%. However, the number of spontaneously active 5-HT neurons per microelectrode trajectory through the dorsal raphe or their average rate of firing was unaltered. The effect of afferent 5-HT pathway stimulation was reduced in only 40% of treated rats, whereas the sensitivity of CA3 pyramidal neurons to microiontophoretic 5-HT was not modified. The function of the terminal 5-HT autoreceptor was assessed using methiothepin, an autoreceptor antagonist. Methiothepin (1 mg/kg, i.v.) significantly enhanced the efficacy of the stimulation in PCPA-treated rats, although the degree of enhancement was much less than in controls. A greater reduction of the effectiveness of the stimulation was obtained by increasing the dose of PCPA (350 mg/kg/day i.p. for 2 days). This regimen reduced the 5-HT content of the dorsal hippocampus by 95%. In these rats, the sensitivity of the terminal 5-HT autoreceptor was assessed by increasing the frequency of the stimulation from 1 to 5 Hz. This procedure reduced to a similar extent the efficacy of the stimulation in treated and control rats, suggesting that the reduced effectiveness of methiothepin in enhancing 5-HT synaptic transmission in PCPA-treated rats is due to a lower degree of activation of the terminal 5-HT autoreceptor. The present results showing that the 350 mg/kg/day regimen of PCPA, but not the 250 mg/kg/day regimen, reduced the efficacy of the stimulation of the ascending 5-HT pathway suggest that a greater than 90% depletion is required to affect 5-HT neurotransmission significantly. The reduced level of activation of terminal 5-HT autoreceptors in rats treated with the lower dose of PCPA may facilitate the release of the remaining 5-HT per stimulation-triggered action potential, ensuring a virtually unaltered synaptic efficacy.

5,7-Dihydroxytryptamine↗
PubMed1990

Differential effect of gepirone on presynaptic and postsynaptic serotonin receptors: single-cell recording studies.

The sustained administration of the serotonin (5-hydroxytryptamine1A, 5-HT1A) agonist gepirone (15 mg/kg/day subcutaneously) in the rat produced an initial decrease of the firing activity of dorsal raphe 5-HT neurons, which was followed by a progressive recovery to normal after 14 days of treatment. At this point, the somatodendritic 5-HT1A autoreceptor had desensitized, as indicated by the reduced effectiveness of intravenous lysergic acid diethylamide (LSD) and of microiontophoretic applications of 5-HT, LSD, 8-hydroxy-2-(N,N-propylamino) tetralin (8-OH-DPAT), and gepirone, but not of gamma-aminobutyric acid in depressing the firing activity of 5-HT neurons. In contrast, the responsiveness of postsynaptic dorsal hippocampus pyramidal neurons to 5-HT, 8-OH-DPAT, and gepirone was not altered by the 14-day gepirone treatment. In an attempt to unravel the differential effect of sustained gepirone administration on presynaptic and postsynaptic 5-HT1A receptors, the properties of gepirone at these two receptors were assessed. The concurrent microiontophoretic application of gepirone readily blocked the effect of 5-HT on dorsal hippocampus pyramidal neurons, but not on dorsal raphe 5-HT neurons, thus indicating that gepirone is a partial agonist at postsynaptic 5-HT1A receptors and a full agonist at somatodendritic 5-HT1A receptors. It is proposed that gepirone, being a partial agonist at postsynaptic 5-HT1A receptors, fails to desensitize them; whereas, because of its full agonistic activity at the somatodendritic 5-HT1A receptor, it desensitizes this autoreceptor with long-term administration.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Electrophysiological investigation of the adaptive response of the 5-HT system to the administration of 5-HT1A receptor agonists.

The effects of acute and long-term administration of 5-HT1A agonists were studied in vivo in the rat brain. Unitary extracellular recordings were obtained from dorsal raphe 5-HT neurons and dorsal hippocampus pyramidal neurons. Gepirone and 8-OH-DPAT, two 5-HT1A agonists, when administered intravenously or applied by microiontophoresis, dose-dependently decreased the firing rate of these 5-HT neurons. Gepirone acted as a full agonist at the somatodendritic 5-HT autoreceptor, which is of the 5-HT1A subtype. Microiontophoretic application of gepirone also decreased the firing activity of postsynaptic hippocampus pyramidal neurons. At these postsynaptic 5-HT1A receptors, however, gepirone acted as a partial agonist. A 2-day treatment with gepirone markedly reduced the firing rate of 5-HT neurons; this was followed by a partial recovery after 7 days of treatment and a complete one after 14 days of treatment. This adaptation of 5-HT neurons was attributable to a desensitization of their somatodendritic 5-HT autoreceptors. The 14-day treatment with gepirone did not induce a desensitization of 5-HT1A receptors on postsynaptic pyramidal neurons. It is concluded that the sustained administration of a 5-HT1A agonist results in an enhanced tonic activation of postsynaptic 5-HT1A receptors in the forebrain. It can be presumed that the recovery of the firing activity of 5-HT neurons restores a normal release of endogenous 5-HT, upon which the agonistic action of the 5-HT1A agonist on normosensitive postsynaptic 5-HT receptors is superimposed.

Adaptation, Physiological↗
PubMed1990

Neurotoxic effect of domoic acid: mediation by kainate receptor electrophysiological studies in the rat.

Domoic acid, an excitatory amino acid structurally related to kainic acid, has recently been identified as being responsible for the severe intoxication presented, in 1987, by more than 150 people having eaten mussels grown in Prince Edward Island. The present in vivo electrophysiological studies, using unitary extracellular recordings obtained from pyramidal neurons of the CA1 and of the CA3 regions of the rat dorsal hippocampus, were undertaken to study the effect of kainic acid and domoic acid applied by microiontophoresis and compare their potencies to that of agonists of the 2 other subtypes of glutamatergic receptors or neuropeptides. The activation induced by domoic acid and kainate was more than 20-fold more potent in the CA3 than in the CA1 region, whereas no such regional difference could be detected with all the other substances tested. In the CA1 as well as in the CA3 region, domoic acid was about 3 times more potent than kainate. A selective lesion of the mossy fibre system originating from the dentate gyrus and projecting to the CA3 region of the dorsal hippocampus, drastically reduced the excitatory effect of kainic acid and domoic acid in this later area, without affecting the response to the other substances tested. Several class of pharmacological agents were studied in an attempt to find an antagonist of kainate and domoic acid. Only benzodiazepines could selectively suppress the neuronal activation induced by kainate, however, with a lower efficacy in the CA3 than in the CA1 region. These results demonstrate that domoic acid is a potent agonist of kainate receptors and that, in the CA3 region, it might produce its neurotoxic effects through activation of kainate receptors located on mossy fibre terminals. Finally, in the event of a new wave of intoxication, our results suggest that a rapid treatment with high doses of benzodiazepines could possibly prevent the important and irreversible hippocampal damage.

Acetylcholine↗
PubMed1990

Effects of long-term haloperidol treatment on the responsiveness of accumbens neurons to cholecystokinin and dopamine: electrophysiological and radioligand binding studies in the rat.

Cholecystokinin (CCK) and dopamine (DA) coexist in a subpopulation of neurons of the ventral tegmental area projecting to the nucleus accumbens. The present experiments were undertaken to determine the effect of acute and long-term administration of haloperidol on the responsiveness of accumbens neurons to microiontophoretic applications of the sulfated cholecystokinin octapeptide (CCK-8S), kainate (KA), and DA and on the density of CCK, D1, and D2 receptors determined by radioautography. Acute administration of haloperidol (1 mg/kg, i.v.) did not modify the neuronal responsiveness to DA and KA but increased that to CCK-8S. Long-term treatment with haloperidol decanoate (4 mg/kg/week, i.m., for 3-5 weeks) induced a marked increase in the responsiveness to CCK-8S, without noticeable change of that to DA and KA. After a 5 week treatment, significant increases in the amounts of CCK and D2 binding were found in the nucleus accumbens, whereas D1 binding parameters remained unchanged. Since long-term haloperidol treatment results in a depolarization inactivation of A10 dopaminergic neurons, these results suggest that, despite the reduced firing activity of mesolimbic dopaminergic neurons induced by the long-term haloperidol treatment, dopamine is still released in an amount sufficient to maintain a normal neuronal responsiveness of postsynaptic accumbens neurons to DA, whereas the release of CCK is possibly decreased to a greater extent, resulting in an enhanced responsiveness of the neurons to this peptide.

Animals↗
PubMed1990

A role for the serotonin system in the mechanism of action of antidepressant treatments: preclinical evidence.

The electrophysiologic assessment of the action of different types of antidepressant treatments on the serotonin (5-hydroxytryptamine [5-HT]) system revealed as a common effect an enhancement of 5-HT neurotransmission, albeit each treatment achieved this result via a different mechanism. Tricyclic antidepressant drugs and electroconvulsive shock treatment sensitize postsynaptic neurons to 5-HT. Monoamine oxidase inhibitors enhance the availability of releasable 5-HT. Serotonin reuptake blockers increase the efficacy of 5-HT neurons by desensitizing 5-HT autoreceptors located on 5-HT nerve terminals. Serotonin1A receptor agonists would enhance the tonic activation of postsynaptic 5-HT1A receptors. Such results suggest that this effect of antidepressant treatments on the 5-HT system might be intimately related to their therapeutic effect in major depression.

Antidepressive Agents, Tricyclic↗
PubMed1990

Benzodiazepine receptors modulate 5-hydroxytryptamine neurotransmission in the rat hippocampus: in vivo electrophysiological evidence.

In the present electrophysiological studies the effects of the activation of putative presynaptic benzodiazepine receptors (BZR) in modulating serotonergic (5-HT) transmission in dorsal hippocampus were investigated in chloral hydrate-anesthetized rats. The effectiveness of the electrical stimulation of the ascending 5-HT pathway on the firing activity of CA3 hippocampus pyramidal neurons was modulated by the intravenous administration of BZR ligands. The BZR agonists, diazepam, lorazepam and CL 218,872, dose-dependently enhanced the effectiveness of the stimulation. In contrast, the BZR inverse agonist, FG 7142, dose-dependently decreased it. The effects of agonist and inverse agonist BZR ligands were blocked by the specific BZR antagonist flumazenil. Diazepam and FG 7142 did not modify the efficacy of microiontophoretic applications of gamma-aminobutyric acid and 5-HT onto hippocampal CA3 neurons. BMY 7378, a 5-HT1A receptor antagonist which blocks the effect of the endogenous 5-HT released by the electrical stimulation of 5-HT fibers in this paradigm, also blocked the enhancing action of diazepam on the effectiveness of the stimulation. These results indicate that the activation of BZR of type I modulates 5-HT neurotransmission, presumably through a presynaptic regulatory mechanism.

Animals↗
PubMed1990

Modification of serotonergic neuron properties by long-term treatment with serotonin reuptake blockers.

The authors investigated the mechanism of action of the antidepressant serotonin (5-HT) reuptake blocker citalopram in the rat by means of an in vivo electrophysiologic paradigm. In control animals, the acute intravenous administration of citalopram reduced the firing rate of dorsal raphe nucleus serotonergic neurons with an ED50 of 230 micrograms/kg. Rats were treated with citalopram (20 mg/kg/day i.p.) for 2, 7, and 14 days. Two-day treatment was accompanied by a marked reduction of the firing activity of serotonergic neurons; there was a partial recovery after 7 days of treatment, and a complete one following 14-day citalopram administration. The response of serotonergic neurons to intravenously administered lysergic acid diethylamide (LSD), a somatodendritic 5-HT autoreceptor agonist, was reduced in rats treated with citalopram for 14 days, suggesting that such a treatment reduces the sensitivity of the somatodendritic autoreceptor. Fourteen-day citalopram treatment also markedly enhanced the efficacy of the stimulation of the afferent serotonergic pathway in suppressing the firing activity of postsynaptic CA3 dorsal hippocampus pyramidal neurons. This enhanced efficacy of serotonergic synaptic transmission was not the result of an increased sensitivity of postsynaptic neurons to serotonin, as the effect of the direct microiontophoretic application of serotonin onto these same neurons was not modified. That serotonin reuptake blockade per se was responsible for this enhancement could also be ruled out, as the acute intravenous administration of citalopram (1 mg/kg) in control rats failed to enhance the efficacy of the stimulation. To determine an involvement of the 5-HT terminal autoreceptor, methiothepin (1 mg/kg), a terminal autoreceptor antagonist, was injected intravenously in control and citalopram-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hippocampal mossy fiber denervation induces a supersensitivity to cholecystokinin of CA3 pyramidal neurons in the guinea pig but not in the rat.

Immunohistochemical studies have revealed the presence of cholecystokinin (CCK) in the guinea pig hippocampal mossy fiber projections, but this peptide appears to be absent in this system in the rat. However, in both species the mossy fiber system shows a strong opiate-like immunoreactivity. The present electrophysiological studies were undertaken to determine, in the two species, the effect of a unilateral colchicine-induced mossy fiber denervation, by comparing the responsiveness of target pyramidal neurons to Met-enkephalin, CCK and the nonpeptidic excitatory agents acetylcholine, kainate, quisqualate and ibotenate, on the intact and on the lesioned side. In both species, the colchicine lesion induced an increased responsiveness to Metenkephalin in the CA1 area, whereas no change was found in the neuronal responsiveness to the other excitatory agents tested. In the rat, the responsiveness of CA3 pyramidal neurons to kainate was reduced by 90%, those to the other excitatory agents were unchanged. In the guinea pig, the mossy fiber denervation induced a 10-fold increase of the responsiveness of CA3 pyramidal neurons to CCK, but did not modify their response to Met-enkephalin, kainate, quisqualate, ibotenate and acetylcholine. These results are consistent with the lack of CCK-like immunoreactivity in the mossy fiber projection to the CA3 region of the rat and with previous reports suggesting the presynaptic location of kainate receptors in this region. They provide novel evidence for the physiological role of CCK in the hippocampal mossy fiber projection in the guinea pig.

Animals↗
PubMed1989

Electrophysiological characterization of adrenoceptors in the rat dorsal hippocampus. III. Evidence for the physiological role of terminal alpha 2-adrenergic autoreceptors.

The present electrophysiological studies were undertaken to assess the role of terminal alpha 2-adrenergic autoreceptors in regulating noradrenergic synaptic transmission in the rat CNS. The effectiveness of the electrical stimulation of the locus coeruleus (LC) in suppressing the firing activity of pyramidal neurons was determined in the dorsal hippocampus. Intravenous clonidine, an alpha 2-adrenergic agonist, decreased the effectiveness of the LC stimulation, without altering the effect of microiontophoretically applied norepinephrine. The subsequent i.v. administration of low doses of idazoxan, an alpha 2-adrenergic antagonist, reversed this effect of clonidine on the LC stimulation. To ascertain that the effect of clonidine administered i.v. was indeed attributable to its action on noradrenergic terminals, it was applied locally by microiontophoresis; it decreased the effectiveness of the LC stimulation. Another paradigm used to assess the function of terminal alpha 2-adrenoceptors was to increase the frequency of the LC stimulation from 1 to 5 Hz. This resulted in a 5-fold decrease of the effectiveness of the stimulation. That this was attributable to an enhanced activation of terminal alpha 2-adrenoceptors was suggested by the reversal of this effect of increasing the frequency of the LC stimulation by intravenous idazoxan. Furthermore, the degree of enhancement of the effectiveness of the LC stimulation by idazoxan was much greater at 5 than at 1 Hz. These results provide novel electrophysiological evidence for the potent regulatory role of terminal alpha 2-adrenoceptors on noradrenergic neurotransmission.

Action Potentials↗
PubMed1989

Cholecystokinin tetrapeptide induces panic-like attacks in healthy volunteers. Preliminary findings.

A total of 31 intravenous injections of the tetrapeptide cholecystokinin (30-33) were carried out in ten healthy subjects. In seven subjects, cholecystokinin-4 provoked a short-lasting (one to four minutes) panic-like attack (an intense unexplainable fear) at doses between 20 and 100 micrograms. In the other three subjects, doses of 80 to 100 micrograms induced severe anxiety, but no panic-like attack. All subjects experienced severe gastrointestinal symptoms. Pretreatment with lorazepam, but not with meprobamate or naloxone, prevented the psychic effects of cholecystokinin-4 in subjects who had experienced a panic-like attack with the same dose of this peptide. Following the peptide injection, levels of plasma free catecholamines, lactate, and glucose were unchanged, whereas levels of plasma cortisol and prolactin were increased. The intravenous injection of the sulfated cholecystokinin octapeptide (26-33) in two subjects (doses of 35 and 40 micrograms, respectively) produced severe gastrointestinal symptoms, but failed to induce any anxiety or panic-like attacks. These preliminary findings suggest that cholecystokinin-4 may have a panic-inducing effect. It remains to be established if this peptide exerts this effect via a direct activation of central cholecystokinin receptors.

Adult↗