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E Mogilnicka

Publications and source records attributed to E Mogilnicka.

At least 19 recordsLinked to original sources
PubMed1991

Some central pharmacological effects of the calcium channel antagonist flunarizine.

Our earlier studies showed that dihydropyridine calcium channel antagonists have some central pharmacological effects. Flunarizine is considered to be a calcium channel antagonist; therefore this study was aimed at investigating the effect of flunarizine (given in single doses of 5, 10 and 20 mg/kg p.o.) in behavioural models in which calcium channel antagonists of the dihydropyridine type were previously studied. Flunarizine inhibited the apomorphine-induced stereotypy and yawning behaviour in rats. It decreased the hypothermia induced by a low dose of apomorphine in mice, but not that one induced by high dose of it. The quinpirole-induced hypothermia was also reduced. In the tests used for evaluation of the effect on the serotonergic system, flunarizine decreased the 5-HTP-induced head twitches and partly antagonized the fenfluramine- and quipazine-induced hyperthermias (at a high ambient temperature). In the forced swimming test flunarizine was inactive in mice and rats. The obtained results indicate that flunarizine exerts central antagonistic effects on the dopaminergic and serotonergic systems and has no antidepressant activity. Flunarizine differs from calcium channel antagonists of the dihydropyridine type, which have no dopamine-antagonistic activity and show anti-depressant-like properties.

5-Hydroxytryptophan↗
PubMed1990

Antidepressant-like activity of the melatonin receptor antagonist, luzindole (N-0774), in the mouse behavioral despair test.

The anti-immobility effect of the selective melatonin receptor antagonist, luzindole, was investigated in the behavioral despair test using three different strains (C3H/HeN, C57BL/6J and albino ND/4) of mice. The time of immobility of the C3H/HeN during the 240 s swimming period measured at noon (12:00 to 14:00 h) was 47.8 +/- 3.0 s (n = 63) and at midnight (00:00 to 02:00 h) was 67.7 +/- 2.8 s (n = 68) (P less than 0.001, when compared with the noon value), when the levels of endogenous melatonin are presumably low and high, respectively. Melatonin (30 mg/kg) given i.p. did not modify the time of immobility at either time of measurement. Luzindole (30 mg/kg i.p.) reduced the time of immobility in a dose-dependent manner, the effect being more pronounced at midnight (60% reduction) than at noon (39% reduction). The effect of luzindole was time-dependent, showing a maximal effect at 60 min. The anti-immobility effect of luzindole (10 mg/kg i.p.) was prevented by the administration of melatonin (30 mg/kg i.p.). Luzindole (30 mg/kg i.p.) did not modify the time of immobility either at noon or midnight in the albino ND/4 mouse, or in the C57BL/6J mouse, which does not produce melatonin. Our results suggest that endogenous melatonin plays a role during swimming in the C3H/HeN mouse behavioral despair test. We conclude that luzindole may exert antidepressant-like activity in the C3H/HeN mouse by antagonizing the action of endogenous hormone.

Animals↗
PubMed1990

Some behavioral effects of repeated administration of calcium channel antagonists.

The effect of the calcium channel antagonists nifedipine, nimodipine, and diltiazem (10 mg/kg PO) was studied after single and repeated administration to rats. All the compounds administered repeatedly reduced significantly the duration of immobility in the forced swimming test. At the same time the locomotor activity of rats was reduced (nifedipine, nimodipine) or unchanged (diltiazem). All the calcium channel antagonists studied did not modify the behavior of normal or phenylephrine-stimulated rats in the open field test. Only nimodipine, given repeatedly, was able to antagonize the clonidine-induced behavioral inhibition in the latter test. The results indicate that, like antidepressants, calcium channel antagonists given repeatedly to rats reduce the immobility time in the forced swimming test, but do not change the responsiveness of alpha 1- and alpha 2-adrenoceptors to their agonists.

Animals↗
PubMed1989

Dihydropyridine calcium channel antagonists as antidepressant drugs in mice and rats.

A pharmacological profile of the effects of nimodipine, nifedipine and nitrendipine (2.5-20 mg/kg p.o.) in several models which are indicative of possible antidepressant activity, was tested in mice and rats. These compounds, as well as verapamil (short-lasting effect), but not diltiazem, reduced the hypothermia induced by a large dose of apomorphine in mice. Nimodipine and nifedipine slightly increased the behavioural action of L-DOPA in mice, and nimodipine facilitated the action of imipramine in the L-DOPA test. Nimodipine, nifedipine, verapamil and diltiazem slightly reduced the clonidine-induced hypoactivity in rats. The hypothermia induced by reserpine or clonidine in mice was not changed by these drugs. Various antidepressants (imipramine, amitriptyline, citalopram, mianserin) used in the behavioural despair test in mice, in doses which were not effective by themselves, increased the immobility-reducing effect when given jointly with 1,4-dihydropyridine calcium channel antagonists (5 mg/kg). The above results indicate that the psychopharmacological profile of nimodipine, nifedipine and nitrendipine resembles that of antidepressants in some tests only; moreover, these results support the assumption that concomitant administration of antidepressants and 1,4-dihydropyridine calcium channel antagonists may result in a greater antidepressant efficacy.

Animals↗
PubMed1988

Effect of nifedipine on the shuttlebox escape deficit induced by inescapable shock in the rat.

The behavioural effect of subchronic treatment with calcium channel antagonists (nifedipine, verapamil) and with imipramine was assessed in rats subjected to inescapable shock (IS). The effect of subchronic treatment with nifedipine and imipramine on specific [3H]nitrendipine ([3H]NDP) binding was investigated in frontal cortex of naive rats and in rats given IS then tested for shuttlebox escape. The rats showed a severe impairment in escape behaviour after IS. Imipramine and nifedipine significantly reduced FR1 and FR2 escape deficits. Verapamil had no effect. A small but significant increase in the number of [3H]NDP binding sites (Bmax) was seen in rats exposed to the shuttlebox escape test independent of a previous exposure to IS. Imipramine had no influence on Bmax in any of the groups. Nifedipine did not affect [3H]NDP binding in naive rats but decreased Bmax in rats subjected to IS and the shuttlebox escape test. The comparable ability of nifedipine and imipramine to reverse the shuttlebox escape deficit induced by IS argues for a possible antidepressant activity of nifedipine. The biochemical data indicate that cortical [3H]NDP binding sites are not correlated to performance in the shuttlebox escape test.

Animals↗
PubMed1988

BAY K 8644 enhances immobility in the mouse behavioral despair test, an effect blocked by nifedipine.

The effect of the dihydropyridine calcium channel agonist, BAY K 8644 (0.05, 0.1, 0.5 mg/kg i.p.), in the mouse behavioral despair test was investigated. BAY K 8644 dose dependently prolonged the duration of immobility. The BAY K 8644 (0.1 mg/kg)-induced prolongation of immobility was antagonized by the dihydropyridine calcium channel antagonist, nifedipine, but not by the non-dihydropyridine type antagonists, verapamil and diltiazem. The effect of BAY K 8644 was also antagonized by desipramine and imipramine but not by citalopram and iprindole. Therefore we suggest that central dihydropyridine binding sites play a role in despair behavior.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Single treatments with the antidepressant oxaprotiline and its (+) and (-) enantiomers increase behavioural responses to dopaminergic stimulation in the rat.

The effects of single doses of oxaprotiline and its (+)- and (-)-enantiomers (CGP 12 104 A and CGP 12 103 A, provisional generic name levoprotiline) on apomorphine- and amphetamine-induced stereotypies and amphetamine-induced hyperthermia were investigated in the rat. All 3 compounds enhanced and prolonged stereotyped responses to apomorphine and amphetamine at single doses of 10-30 mg/kg i.p. The most active appeared to be the (-)-enantiomer levoprotiline which is devoid of NA-uptake-inhibiting properties. Neither compound, however, potentiated amphetamine-induced hyperthermia, suggesting that enhanced behavioural effects are not due to the interference with metabolic degradation of amphetamine. The mechanism of the observed effect remains obscure, but in view of the reported clinical antidepressant action of levoprotiline these findings are interesting.

Animals↗
PubMed1987

Dihydropyridine calcium channel antagonists reduce immobility in the mouse behavioral despair test; antidepressants facilitate nifedipine action.

The effect of the calcium channel antagonists nifedipine, nitrendipine, nimodipine, verapamil and diltiazem in the mouse behavioral despair test was investigated. The dihydropyridine calcium channel antagonists nifedipine, nitrendipine, nimodipine (0.1, 1, 10 mg/kg p.o.) but not the non-dihydropyridine compounds verapamil or diltiazem, dose dependently reduced immobility. Various antidepressant drugs (imipramine, mianserin, citalopram, (+)oxaprotiline) and (-)oxaprotiline in combination with nifedipine facilitated its effect.

Animals↗
PubMed1987

Functional supersensitivity to the alpha 1-adrenoceptor agonist after repeated treatment with antidepressant drugs is not conditioned by beta-down-regulation.

The effect of repeated administration of desipramine, and the (+)- and (-)-enantiomers of oxaprotiline (10 mg/kg i.p., twice daily for 14 days) on the binding of beta- and alpha 1-adrenoceptors in the cortex of the rat brain were studied. The functional consequences of such treatment were measured in a behavioural model, involving the exploratory activity of rats in response to administration of the alpha 1-agonist phenylephrine. Desipramine and (+)-oxaprotiline decreased the binding of [3H]dihydroalprenolol ([3H]DHA) to beta-adrenoceptors in the cortex, did not change the binding of [3H]prazosin to alpha 1-adrenoceptors, but enhanced behavioural responses to phenylephrine. A behavioural facilitation was also observed after administration of (-)-oxaprotiline, a substance which does not change the binding of [3H]DHA. These results indicate that a functional supersensitivity to the alpha 1-adrenoceptor agonist, after repeated treatment with antidepressants is not conditioned by beta-down-regulation.

Adrenergic alpha-Agonists↗
PubMed1986

Deprivation of REM sleep in the rat and the opioid peptides beta-endorphin and dynorphin.

Effects of 'rapid eye movement' sleep deprivation (REMd) on two opioid peptides, beta-endorphin and dynorphin, were studied in rats. Both peptides were measured by radioimmunoassay techniques. The level of beta-endorphin was estimated in the hypothalamus, in the anterior lobe of the pituitary and in the blood. The amount of dynorphin was estimated in the hypothalamus. REMd was induced for 72 h and achieved by two different methods, the platform technique and the pendulum technique. Three control groups were additionally run. As a consequence of REMd, an increase in beta-endorphin level was discovered in the blood plasma, while a small decrease was found in the hypothalamus. No changes could be detected for beta-endorphin levels in the pituitary or for hypothalamic dynorphin concentration. The deprivation effects are interpreted as belonging to a group of changes, all of which point to a small increase in tonic arousal as a result of REMd.

Animals↗
PubMed1986

Repeated treatment with clenbuterol produces desensitization of rat brain beta- and alpha 2-adrenoceptors without changes of alpha 1-adrenoceptors.

The effects of single and repeated administrations of the beta-agonist, clenbuterol (0.5 mg/kg i.p., twice daily for 4 or 7 days) were measured in the open-field test as responsiveness of rats to beta- (clenbuterol), alpha 2-(clonidine) and alpha 1-(phenylephrine) adrenergic stimulation. Furthermore, the effects of such treatment on beta- and beta 1-adrenoceptor binding in the rat brain cortex were studied. Repeated administration of clenbuterol failed to change the exploratory activity, in contrast to the acute sedative effect. Repeated treatment with clenbuterol resulted in a decrease in [3H]dihydroalprenolol binding to cortical beta-adrenoceptors. A single dose of clenbuterol reduced the clonidine-induced sedation and repeated treatment of clenbuterol abolished this sedation. Clenbuterol did not affect the action of phenylephrine nor did it change the binding of [3H]prazosin. These results indicate that repeated administration of a beta-agonist produces a rapid appearance of beta- and alpha 2-adrenoceptor subsensitivity, which it not followed by alpha 1-adrenoceptor changes.

Animals↗
PubMed1986

Desipramine induces yawning behaviour in rats.

Yawning behaviour in rats injected subcutaneously with antidepressant drugs was studied by direct observation. Desipramine (0.1-30 mg/kg) elicited yawning that began 15-20 min after injection and lasted for 60 min, and the dose-response curve showed a bell-shaped form. Desipramine (10 mg/kg) elicited the maximal effect (mean number of yawns 13.6). Haloperidol (0.02 mg/kg), spiperone (0.2 mg/kg), pimozide (4 mg/kg), reserpine (7.5 mg/kg), alpha-methyl-p-tyrosine (250 mg/kg) and scopolamine (0.5 mg/kg) markedly reduced yawning induced by desipramine, whereas prazosin (1 mg/kg) and phenoxybenzamine (5 mg/kg) were without effect. These findings indicate that desipramine induces yawning by a dopaminergic mechanism, and that endogenous dopamine (DA) is necessary for its occurrence. Yawning was observed also after administration of imipramine, clomipramine, trazodone, its metabolite m-chlorophenylpiperazine and (+/-)sulpiride. These drugs given in a similar dose-range to desipramine produced a weaker effect than desipramine. Selective and potent inhibitors of the uptake of noradrenaline (NA) or 5-hydroxytryptamine (5-HT), (+)oxaprotiline and citalopram, did not elicit yawning. A possibility is considered that certain antidepressant drugs induced yawning through an influence on dopaminergic system.

Animals↗
PubMed1986

Age-dependent day/night variations of alpha 1- and beta-adrenoceptors in the rat cerebral cortex.

Receptor binding studies in the cerebral cortex of young (2-4 months) and mature (11-12 months) rats were conducted at two points of the circadian time: 8.00 and 20.00 hr. In addition, the exploratory activity in the open field was assessed. In young rats the density of alpha 1- and beta-adrenoceptors increased at 20.00 in comparison with 8.00 hr, while no changes in the exploratory activity were observed. However, in mature rats the activity was higher at 20.00 than 8.00 hr; at the same time, a rise in the density of alpha 1- but not beta-adrenoceptors was observed. Obtained data suggest that the increased exploratory activity of mature rats at 20.00 hr may appear as a result of a higher density of alpha 1-adrenoceptors and a simultaneous lack of changes in beta-adrenoceptors.

Aging↗
PubMed1986

Effects of REM sleep deprivation on central alpha 1- and beta-adrenoceptors in rat brain.

In the present experiment the effects of 'rapid-eye-movement' sleep deprivation (REMd) on cortical alpha 1- and beta-adrenoceptor binding sites in the rat brain were investigated. REMd was induced for 72 hr in two different ways: by the platform and the pendulum technique. In addition, three control groups were run. Determination of alpha 1- and beta-adrenoceptor sites in the cortex was done by 3H-prazosin and 3H-dihydroalprenolol binding studies, respectively. Both REM sleep deprived groups showed a small but significant decrease in the number of beta-adrenoceptor sites along with a small increase in affinity. On the other hand, alpha 1-adrenoceptor binding and affinity were not changed. These results agree with the effects of tricyclic antidepressant drug treatment. Common effects of REMd and tricyclic drugs are discussed in terms of modulation of tonic arousal processes.

Animals↗
PubMed1986

Increase in beta- and alpha 1-adrenoceptor binding sites in the rat brain and in the alpha 1-adrenoceptor functional sensitivity after the DSP-4-induced noradrenergic denervation.

Changes in the density of beta- and alpha 1-adrenoceptors were studied following denervation of the rat cerebral cortex and hippocampus, caused by systemic administration of DSP-4. The noradrenergic denervation increased both beta- and alpha 1-adrenoceptor density by about 30 and 17%, respectively in the cortex, and by about 30% in the hippocampus. In order to estimate the behavioral response of normal and DSP-4-treated rats to alpha 1-agonist, the influence of phenylephrine (25 micrograms ICV) on the exploratory activity of rats in the open field was measured. Phenylephrine failed to change the exploratory activity of normal rats, but significantly increased it in DSP-4 animals. The results indicate that noradrenergic denervation produces an increase in number of both beta- and alpha 1-adrenoceptors and the functional supersensitivity to the alpha 1-adrenergic agonists.

Animals↗
PubMed1985

The importance of timing for the action of alpha 1- or beta-agonists: possible relationship with the density of [3H]prazosin and [3H]dihydroalprenolol binding sites.

Exploratory behaviour was measured in the open-field at 8.00 h and 20.00 h with naive rats and rats treated with an alpha 1-agonist (phenylephrine, 25 micrograms i.c.v.) or beta-agonists (salbutamol, 2.5 mg/kg; clenbuterol 0.05 mg/kg i.p.). The spontaneous activity was similar at both times, yet the response to a alpha 1-as well as to beta-stimulation was significantly enhanced at 20.00 h. The density of cortical [3H]prazosin and [3H]dihydroalprenolol ([3H]DHA) binding sites at 20.00 h was enhanced by 19% and 28% respectively, in comparison with the density measured at 8.00 h.

Adrenergic alpha-Agonists↗