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H Frances

Publications and source records attributed to H Frances.

At least 19 recordsLinked to original sources
PubMed1994

Behavioral effect of beta-blocking drugs resulting from the stimulation or the blockade of serotonergic 5-HT1B receptors.

The present study was aimed at determining the relative potency of various beta-blocking drugs as agonists or antagonists at 5-HT1B receptors. The behavioral model used (increase in escape attempts of isolated mice) has been previously shown to be exclusively responsive to 5-HT1B agonists such as 1-3-(trifluoromethyl) phenylpiperazine (TFMPP). Beta-blocking drugs acted in three different ways: they were either inactive, or acted as agonists or as antagonists at 5-HT1B receptors. The specific beta-blocking drugs: atenolol and betaxolol (beta-1) and ICI 118,551 (beta-2) were inactive by themselves and in interaction with TFMPP. The mixed beta-1 beta-2 blocking drug 1-penbutolol, (but not d-penbutolol), inactive alone, behaved as an antagonist: it impaired in a dose-dependent way the effect of TFMPP. (+/-)Pindolol and (-)pindolol was inactive. None of the (-), (+), or (+/-)pindolol was able to impair TFMPP effect. The increase in escape attempts induced by (+/-)pindolol was antagonized with 1-penbutolol or after a specific desensitization. Cyanopindolol and S-tertatolol (but not R-tertatolol) acted as agonists. SDZ 21009 was inactive as agonist or antagonist. It may be concluded that all beta-blocking drugs are not equivalent regarding their effect at 5-HT1B receptors. L-penbutolol was the only drug acting as an antagonist.

Adrenergic beta-Antagonists↗
PubMed1992

Behavioral tolerance to one effect of the serotonergic agonist TFMPP.

1. In mice isolated for one week and observed in pairs with non-isolated mice under a reversed beaker, the serotonergic agonist: 1-3-(trifluoromethyl)phenylpiperazine (TFMPP) increased the number of escape attempts. 2. A partial tolerance to this effect has been observed in mice which were tested a first time after administration of TFMPP one week sooner. 3. An analysis of this form of tolerance was carried out by changing successively and separately each of the events concomitant of this tolerance. 4. The results show that this tolerance is not a pharmacocinetic or a pharmacodynamic one. Observation of the tolerance required the performance of the first test in a drug state. The more likely explanation is that this tolerance results from a conditioned opponent response.

Animals↗
PubMed1991

Tolerance to the behavioural effect of serotonergic (5-HT1B) agonists in the isolation-induced social behavioural deficit test.

In mice, isolation-induced social behavioural deficits are attenuated by stimulants of 5-HT1B receptors, such as TFMPP or CGS 120 66B. Repeated treatment with RU 24969 (5 mg/kg, daily, for 3 days) reduced the effect of TFMPP and that of other 5-HT1B agonists (CGS 120 66B, m-CPP, RU 24969). Similarly, repeated treatment with CGS 120 66B (8 mg/kg, twice a day for 3 days) abolished the effect of a test-dose of the same drug. Desensitization of the 5-HT1B receptors involved in this effect is suggested to have occurred. Such a desensitization may be therapeutically relevant, since acute administration of benzodiazepines and chronic administration of antidepressants both reversed the effect of TFMPP.

Animals↗
PubMed1991

Isolation increases a behavioral response to the selective 5-HT 1B agonist CGS 120 66B.

The effect of two serotonergic drugs, CGS 120 66B acting specifically and TFMPP acting preferentially onto 5-HT1B receptors, was compared in preisolated and in pregrouped mice. Two mice put under an inverted beaker attempt to escape. The number of escape attempts of mice preisolated for 7 days was half that of pregrouped mice. In preisolated mice, TFMPP and CGS 120 66B increased the number of escape attempts up to, respectively, 200% and 300% of that of preisolated control mice. In pregrouped mice, CGS 120 66B was nearly inactive and TFMPP exerts a smaller effect. These results suggest that isolation increases the apparent responsiveness to 5-HT1B stimulants.

Animals↗
PubMed1990

Chronic but not acute antidepressants interfere with serotonin (5-HT1B) receptors.

Eight days of isolation induced in mice a social behavioral deficit responsive to the serotonin agonists, TFMPP (1-(m-trifluoromethylphenyl)piperazine), m-CPP (1-(3-chlorophenyl)piperazine), RU 24969. These drugs are not specific for one subtype of serotonin receptors but share the property of being able to stimulate 5-HT1B receptors. They exert their effects in this test through this receptor. Fluoxetine and phenelzine were behaviorally inactive and did not impair the TFMPP effect when given acutely. On the contrary, the chronic administration of these two antidepressant drugs significantly antagonized the TFMPP effect. These results demonstrate a link between two antidepressant drugs and a function of 5-HT1B receptors. The lack of effect of acute versus chronic treatments suggests the involvement of 5-HT1B receptors in the therapeutic effect of these drugs.

Animals↗
PubMed1990

Improvement of the isolation-induced social behavioural deficit involves activation of the 5-HT1B receptors.

1. Mice were isolated for 7-9 days. An isolated mouse and a mouse reared in group showed a difference in their behaviour when observed together under an inverted beaker. The isolated mouse makes one half escape attempts in regard to the grouped mouse. This is considered as a social behavioural deficit. 2. 1- 3-(trifluoromethyl)phenyl piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (m-CPP) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) 1-H indole (RU-24969) activating preferentially the 5-HT1B receptors increased the number of escape attempts of the isolated mice up to the level of grouped mice. 3. Penbutolol, a beta-blocking drug acting also at 5-HT1 receptors, devoid of effect when given alone, antagonized significantly and dose-dependently the effects of TFMPP, m-CPP and RU-24969. 4. The interaction between TFMPP and five various serotonin antagonists was examined. Neither the 5-HT2 receptor antagonist ritanserine, the 5-HT3 receptor antagonist ICS 205-930, the 5-HT1C receptor antagonists mianserin and cyproheptadine antagonized the effect of TFMPP. The neuroleptic spiperone decreased by itself the number of escape attempts and opposed the TFMPP effect. 5. Taken together, these results suggest that the isolation-induced social behavioural deficit may be considered as a behavioural model responsive to 5-HT1B agonists.

Animals↗
PubMed1989

Isolation-induced social behavioral deficit: a proposed model of hyperreactivity with a behavioral inhibition.

The behavior of mice isolated for 7-9 days (isolated mice) was compared to that of mice reared in groups (grouped mice). The method consisted of counting the number of escape attempts of the mice placed under an inverted beaker. When individually observed the isolated mice attempted to escape slightly but significantly more often than the grouped mice. When a pair of mice (one isolated + one grouped) were tested together, the number of escape attempts of the isolated mice was half of that of the grouped mice: this phenomenon was named the isolation-induced social behavioral deficit. These opposed behaviors may mean the same thing: an hyperreactivity to the novelty. In a variety of new situations under the beaker (presence of a lifeless object, of a grouped mouse or of an isolated mouse), the isolated mice were more reactive than the grouped mice. In conclusion, the social behavioral deficit test may be seen as a model of hyperreactivity with a behavioral inhibition.

Animals↗
PubMed1989

Isolation-induced social behavioral deficit test: effect of tranquilizing drugs.

Mice were reared in isolation for one week. Then, one isolated and one group-reared mouse were observed together under an inverted beaker for two minutes. The number of escape attempts of the isolated mouse were half of those of the grouped mouse. This is considered as a social behavioral deficit. The present study was undertaken to assess the effect of neuroleptics and various anxiolytic agents on this behavioral deficit. Neither acute administration of chlorpromazine, levomepromazine, sulpiride, flupentixol, pipotiazine, pimozide and haloperidol nor the subchronic (5 days) administration of flupentixol, pipotiazine and pimozide impaired the behavioral deficit. Diazepam and triazolam increased, chlordiazepoxide, hydroxyzine and buspirone did not modify the behavioral deficit. It is concluded that neuroleptics and anxiolytic agents did not impair the isolation-induced social behavioral deficit either because of inadequate doses or duration of administration or because this behavioral state is unresponsive to neuroleptics and anxiolytic agents.

Animals↗
PubMed1989

Effect of tricyclic antidepressant drugs in the isolation-induced social behavioural deficit test.

1. Mice were isolated for 7-9 days. An isolated mouse and a mouse reared in group show a difference in their behaviour when observed together under an inverted beaker. The isolated mouse makes one half escape attempts in regard to the grouped mouse. This is considered as a social behavioural deficit. 2. The effect of four tricyclic antidepressant drugs was tested on this social behavioural deficit. None of the following drugs acutely given: imipramine, desipramine, amitriptyline impaired the social behavioural deficit. Clomipramine reduced the deficit at the only dose of 2 mg/kg. The four antidepressants tended to increase the deficit at the high dose of 32 mg/kg but this may reflect a sedative effect. Chronic amitriptyline did not impair the social behavioural deficit. 3. It is concluded that acute and probably also chronic antidepressant treatments are without effect on the isolation induced social behavioural deficit test.

Amitriptyline↗
PubMed1988

Psychopharmacological profile of 1-(m-(trifluoromethyl) phenyl) piperazine (TFMPP).

The effect of TFMPP, an agonist of the 5-HT1b receptors, was studied in mice on several psychopharmacological parameters. In contrast to imipramine-like drugs, TFMPP neither antagonized reserpine-induced hypothermia nor increased yohimbine-induced toxicity. Similarly to imipramine-like drugs, TFMPP antagonized oxotremorine-induced hypothermia and was active in the behavioural despair test. In addition, TFMPP normalized a social behavioural deficit induced by isolation. The effects of TFMPP on oxotremorine-induced hypothermia in the behavioural despair test and in the isolation-induced social behavioural deficit are all antagonized by d-1 propranolol. It is concluded that TFMPP seems to possess psychotropic activity resembling only in part that of imipramine-like drugs and that these actions may be mediated through 5-HT1b receptors.

Animals↗
PubMed1987

Beta-adrenergic agonists reduce spontaneous motor activity through either beta 1 or beta 2 receptors.

In mice, the clenbuterol-induced decrease in spontaneous motor activity was antagonized by IPS-339 (beta 2 antagonist) but not by betaxolol (beta 1 antagonist), whereas the isoproterenol-induced decrease in spontaneous motor activity was completely antagonized by betaxolol and only partially by IPS-339. It can be concluded that the clenbuterol-induced decrease in spontaneous motor activity is of the beta 2-type, whereas that induced by isoproterenol is essentially of the beta 1 type. In addition, chronic treatment with clenbuterol induced a tachyphylaxis to the effect of clenbuterol but not of isoproterenol. After chronic administration of tricyclic antidepressants (imipramine and desipramine) the number of cortical beta 1 adrenergic receptors decreased without impairing the clenbuterol-induced decrease in spontaneous motor activity. We conclude that beta 2 adrenergic receptors mediate the clenbuterol-induced decrease in spontaneous motor activity and the tachyphylaxis to this effect after chronic treatment.

Adrenergic beta-Agonists↗
PubMed1986

Chronic beta-adrenergic stimulation increases in mice the sensitivity to methysergide and the number of cerebral high affinity serotonin binding sites (5-HT-1).

Reserpine administration in mice causes, among other effects an akinesia which can be reversed by the serotonin agonist-antagonist methysergide. The effect of methysergide is potentiated by clenbuterol, a beta-adrenergic agonist, which itself causes hypomotility. Potentiation is weak after a single injection of clenbuterol, but becomes much stronger after repeated administration for 12 days. This treatment also causes a 50% increase in the number of high affinity 5-HT-1 binding sites in the brain. This increase would explain the increased potency of methysergide against reserpine-induced akinesia. These results show that: a beta-adrenergic drug, clenbuterol modulates the serotoninergic system; this modulation takes its importance after chronic treatment only; this interrelation may be important in depressive illness since it is observed on a test used in the screening of antidepressant drugs.

Animals↗
PubMed1986

The calcium entry blockers: anti-manic drugs?

The reported property of calcium antagonists as antimanic drugs has been investigated in three models of hyperactivity in mice. The hyperactivity was induced by amphetamine, oxolinic acid or reserpine after inhibition of monoamine oxydase (MAO). Nicardipine (a dihydropyridine derivative) reduces the three hyperactivities, verapamil (a diphenylalkylamine derivative) reduces only oxolinic acid hyperactivity, and diltiazem (a benzothiazepine derivative) was active except in the MAOI-reserpine test. Levomepromazine used as a reference drug reduced the three hyperactivities. The three calcium entry-blockers reduce the different hyperactivities at doses which already decrease motor activity. And so, it seems that their action was not specific. On the contrary, levomepromazine antagonizes MAOI-reserpine induced hypermotility at a dose which is not sedative. These results do not strengthen the property of calcium antagonists as antimanic drugs.

Amphetamines↗
PubMed1985

Comparison of imipramine-imipraminium in mice. To elucidate central or peripheral origin of effects of imipramine.

Imipramine hydrochloride shows effects in a battery of tests used for the screening of antidepressant drugs. The central origin of these pharmacological effects of imipramine has not been clearly established. Imipramine methiodide is a quaternary derivative of imipramine which does not cross the blood-brain barrier easily. The effects of the two forms of imipramine have been compared: on an effect known to have a central origin; on two effects known to have a peripheral origin; on a battery of tests used for the screening of antidepressant drugs. It has been demonstrated that imipramine methiodide is as active as imipramine hydrochloride on two effects of peripheral origin, less active than imipramine hydrochloride on an effect considered to have a central origin and less active than imipramine hydrochloride or inactive on the tests which are used for the screening of antidepressant drugs. Consequently, the tests used for the screening of antidepressant drugs represent, primarily or exclusively, effects of central origin.

Animals↗
PubMed1985

Dissociation of head twitches and tremors during the study of interactions with 5-hydroxytryptophan in mice.

Intraperitoneal injection of 5-hydroxytryptophan and 5-methoxy-N,N-dimethyltryptamine is shown to provoke characteristic behaviors in mice that can be quantified. The two principal phenomena described here are head twitches and tremors. Tremors became more frequent when doses of the two substances studied were increased. Head twitches appeared at lower doses, but beyond a certain dose, they decreased and even disappeared. The effects on these movements of agents that modify serotonin function were then studied. The results pose problems of interpretation that are discussed.

Animals↗
PubMed1984

Stimulation of beta-adrenergic receptors and spontaneous motor activity in mice.

The effects of 3 beta-adrenergic agonists (clenbuterol, isoproterenol and salbutamol) on the spontaneous motor activity of mice were studied. The present research indicated that motor activity was significantly decreased 30 minutes after IP injection of either clenbuterol (0.06 mg/kg), isoproterenol (0.5 mg/kg) or salbutamol (2 mg/kg). Hypomotility induced by clenbuterol was also significantly antagonized by propranolol in doses ranging from 1 to 8 mg/kg and by penbutolol in doses from 0.03 to 0.5 mg/kg. However, practolol, which does not cross the blood brain barrier, did not antagonize the effect of clenbuterol. Therefore, it may be hypothesized that beta adrenergic agonists decrease motor activity by a central mechanism. It was also found that tachyphylaxis or resistance to treatment, observed in cardiovascular and bronchopulmonary systems with beta-adrenergic agonists, developed after 7 injections of clenbuterol (0.25 mg/kg IP, twice daily) in the behavioral model of spontaneous motor activity in mice.

Adrenergic beta-Agonists↗
PubMed1984

Disappearance of the decrease in biting behavior induced by clenbuterol, a beta-adrenergic agonist, after chronic administration.

The beta-adrenergic agonist clenbuterol decreased interest in food in starved mice, 30 minutes after administration. This effect disappeared after repeated treatment with clenbuterol (0.25 mg/kg, twice daily). Three chronic injections were sufficient to prevent the effect of an acute dose of clenbuterol (0.125 mg/kg) up to 45 hours after treatment.

Aggression↗