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Biomedical subjects

E Mogilnicka

Publications and source records attributed to E Mogilnicka.

At least 37 records · Page 2Linked to original sources
PubMed1985

Clonidine and a beta-agonists induce hyperthermia in rats at high ambient temperature.

The effects of the alpha-agonist clonidine and the beta-agonist clenbuterol on body temperature of rats kept at high ambient temperature (28 degrees C) were studied. Both drugs induced a dose-dependent significant increase in temperature. The clonidine-induced hyperthermia was blocked by various alpha 2-antagonists, yohimbine, rauwolscine and RX 781094 and the alpha 1-antagonists, prazosin and corynanthine but not by 1-propranolol, spiperone, metergoline. The hyperthermic effect of clonidine was potentiated in rats after a lesion of the central noradrenergic terminals by DSP-4. The clenbuterol-induced hyperthermia was counteracted by 1-propranolol, yohimbine and rauwolscine but not by atenolol, prazosin, spiperone, metergoline. These observations indicate that clonidine- and clenbuterol-induced hyperthermia is mediated by alpha 2-(postsynaptic) and beta-adrenoceptors, respectively. Moreover, in the latter effect alpha 2-adrenoceptors are involved. The simple temperature measurement can thus be used as a preliminary indicator of central alpha 2- or beta-agonistic properties of the screened drug.

Animals↗
PubMed1985

Adaptive and differential changes on beta- and alpha 2-adrenoreceptors mediated hyperthermia after chronic treatment with antidepressant drugs in the rat kept at high ambient temperature.

We found previously that the beta-agonist clenbuterol and the alpha-agonist clonidine produced hyperthermia in rats kept at high ambient temperature, which effects were mediated by beta- and alpha 2-adrenoceptors, respectively. In the present paper this observation was used for testing the responsiveness of beta- or alpha 2-adrenoceptors, changed by a pharmacological manipulation, i.e., by chronic treatment with antidepressants. The animals were pretreated with desipramine, imipramine or amitriptyline twice a day for 1 or 2 weeks. All antidepressants significantly attenuated the clenbuterol-induced hyperthermia after 2 weeks of treatment. The effect of desipramine was stronger than that of the other antidepressants and appeared as little as 1 week after the treatment. The hyperthermic effect of clonidine was significantly reduced by repeated treatment with desipramine, increased after 2 weeks administration of imipramine, whereas amitriptyline produced no significant changes. In conclusion, these data suggest that, after repeated treatment, the antidepressants tested produce an adaptive decrease in function of beta-adrenoceptors while the same drugs exert differential effects on alpha 2-receptors. Moreover, clenbuterol induced hyperthermia may be a useful test for examining possible functional changes in beta-adrenoceptor sensitivity.

Amitriptyline↗
PubMed1985

Effect of beta-adrenoceptor agonists on apomorphine-induced turning in rats.

The beta-adrenoceptor agonists clenbuterol, salbutamol and formoterol were found to inhibit apomorphine-induced turning behavior in rats with unilateral nigrostriatal lesions. The inhibitory effect of clenbuterol was antagonized by (-)-propranolol, but unaffected by practolol (which does not cross the blood-brain barrier), indicating a central localization of the beta-adrenoceptors mediating the inhibitory effect. A dopamine-releasing activity of clenbuterol did not seem to be responsible for the effect, because known dopamine-releasing agents (amphetamine, methylphenidate) did not antagonize apomorphine-induced turning behavior. Furthermore alpha-methyl-p-tyrosine pretreatment did not prevent the inhibitory effect of clenbuterol. Since L-5-hydroxytryptophan did not mimic the inhibitory effect of clenbuterol, it was concluded that the inhibition of turning behavior is not mediated by the interaction of clenbuterol with the serotonin system. The finding that clenbuterol depressed locomotor activity in the same dose range as it inhibited apomorphine-induced turning tentatively suggests that clenbuterol inhibits apomorphine-induced turning behavior by its central beta-adrenoceptor mediated sedative action.

Adrenergic beta-Agonists↗
PubMed1985

Suppressant effect of REM sleep deprivation on neophobia in normal rats and in rats with selective DSP-4 induced damage of locus coeruleus neurons.

The influence of REM sleep deprivation (REMD) on open field behavior of normal and locus coeruleus (LC)-damaged animals was investigated under the assumption that REMD suppresses neophobia in rats. REMD (for 24 or 72 hr, water tank technique) produced marked changes in behavior of rats encountering a novel object (white cube) in the center of the open field. REMD induced an increase in activity of treated rats; latency to the object approach was shorter, the number of center entries, time spent in object exploration, frequency of ambulation and rearing were significantly higher than in controls, also defecation was nearly abolished. LC-damage (using DSP-4, a selective central noradrenergic neurotoxin) induced neophobic-like reactions manifested by significantly prolonged latency, tendency to decreased object exploration, center entries and reduction of ambulation and rearing. This "neophobic" behavior of DSP-4 rats was counteracted by REMD as well as by subchronic, but not acute treatment, with antidepressant oxaprotiline (2 X daily for 8 days, 10 mg/kg, IP). The results provide strong support for antineophobic activity of REMD. In addition, they indicate possible similarity of REMD and subchronic oxaprotiline action on neophobia-like behavior in rats with damaged LC-neurons.

Animals↗
PubMed1984

Effects of apomorphine, TL-99 and 3-PPP on yawning in rats.

Dopaminergic agonists, apomorphine (APO) (0.025-0.25 mg/kg, s.c.), TL-99 (0.5-3 mg/kg, s.c.) and 3-PPP (0.15-10 mg/kg, s.c.) elicited yawning in rats and the dose-response curves of all 3 compounds showed a bell-shaped form. Haloperidol (0.02 mg/kg, s.c.) reduced the yawning induced by DA-agonists to about 50%. The potencies of the DA-agonists in inducing yawning were APO greater than TL-99 greater than 3-PPP (comparable to potencies obtained in other in vivo tests, determining DA-ergic activity). The findings support the validity of the yawning phenomenon as a screening test for DA-agonists. Additionally, it was found that apomorphine induced yawning was significantly and dose-dependently enhanced by the beta-agonist, formoterol. This effect was counteracted by scopolamine, not changed by metergoline and further increased by l-propranolol. These data support the hypothesis of cholinergic involvement in yawning and indicate a role, though unclear at present, of beta-receptors in this behaviour.

Adrenergic beta-Agonists↗
PubMed1984

Novelty-oriented behavior in the rat after selective damage of locus coeruleus projections by DSP-4, a new noradrenergic neurotoxin.

Open-field behavior and reactions to a novel object (white-colored cube) or a familiar object (drinking bottle) were investigated in rats treated with DSP-4 N-(2-chloroethyl) -N-ethyl-2-bromobenzylamine, a new noradrenergic neurotoxin which selectively damages locus coeruleus projections. Altered behavior in the open-field and in the presence of the novel object (white cube) was observed in DSP-4 rats. This was reflected in decreased exploration-oriented locomotor responses and in longer latencies to approach the novel cube. Also, there was a trend towards fewer center entries and a shorter duration of object exploration. Although these behavioral responses of DSP-4 rats were indicative of enhanced neophobia, other measures of emotionality, such as grooming and defecation, were either unchanged or slightly decreased. Moreover, when the familiar drinking bottle was present in the open-field, water-deprived DSP-4 rats showed no change in any measure of fear including the latency to the first approach and lick, and the duration of the licking episodes. The results of this study suggest that noradrenergic neurons of the locus coeruleus are involved in the regulation of certain, but not all, novelty-oriented responses in the rat. Explorative behavior in the novel environment seems to be particularly dependent on central noradrenaline.

Amines↗
PubMed1983

Altered hindlimb extension in the rat after DSP-4: a useful marker of central noradrenergic depletion.

Rats treated with DSP-4, a selective noradrenergic neurotoxin, usually exhibited an attenuation of hindlimb extension when suspended by the tail. Those animals showing the reduced extension had no post-decapitation reflex (PDR), whereas those animals having a normal extension had the PDR. On this basis, rats injected with DSP-4 can be readily screened for an effective or ineffective noradrenergic lesion. Preliminary evidence suggests that the alpha 2-adrenoceptor is involved in the regulation of hindlimb extension.

Amines↗
PubMed1983

Functional supersensitivity to adrenergic agonists in the rat after DSP-4, a selective noradrenergic neurotoxin.

Rats treated with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenergic neurotoxin, showed no differences compared to control rats in the number of head dips, a measure of exploratory behavior. Since a previous neurochemical investigation had demonstrated that DSP-4 rats have supersensitive alpha 2- and beta-adrenergic receptors in certain regions of the central nervous system, the behavior of these animals was also examined after the injection of clonidine, an alpha 2 agonist, and clenbuterol, a beta agonist. These drugs reduced, in a dose-dependent manner, the head-dipping of both control and DSP-4 rats. However, this effect was of greater magnitude in DSP-4 animals. Control experiments suggested that the response to clonidine and clenbuterol was mediated centrally by alpha 2 and beta receptors, respectively. Other behavioral experiments with agonists of the dopaminergic and serotoninergic systems indicated that these neurotransmitter systems were unchanged in DSP-4 animals. The results are discussed in terms of the selective action of DSP-4 and the responsiveness of DSP-4 rats to adrenergic agonists. The DSP-4-treated rat may constitute a new model of functional supersensitivity to adrenergic agonists.

Amines↗
PubMed1983

Facilitation of shock-induced fighting in the rat after DSP-4, a selective noradrenergic neurotoxin.

Rats treated with DSP-4 showed a marked enhancement of shock-induced fighting (SIF). Administration of 1-propranolol attenuated or completely counteracted SIF in control animals, but only the highest dose (10 mg/kg) of this beta-adrenergic antagonist was effective in reducing SIF in DSP-4 animals. Other behavioral experiments indicated that the responsiveness of DSP-4 rats to dopaminergic, serotoninergic, and cholinergic agonists was unchanged compared to that of control rats. The results confirm the participation of the noradrenergic system in SIF, and substantiate an involvement of beta-adrenergic receptors in this kind of aggression.

5-Hydroxytryptophan↗
PubMed1983

The effects of single and repeated doses of maprotiline, oxaprotiline and its enantiomers on foot-shock induced fighting in rats.

Foot-shock induced fighting behavior (SIF) in rats was tested after single and repeated dose-treatment (10 mg/kg IP twice daily for 10 days) of maprotiline, oxaprotiline and of (+)- and (-)-enantiomers of oxaprotiline. Marked facilitation of SIF was observed after repeated but not single administration of all drugs including the NA-uptake inactive (-)-enantiomer of oxaprotiline. No enhancement of SIF was seen after multiple dose-treatment with promethazine, an antihistaminic, or atropine. The mechanism of the facilitation of SIF induced by antidepressants maprotiline and oxaprotiline as well as by its enantiomers is unclear. The clear-cut dissociation of the effect of (+)- and (-)-oxaprotiline on the rate of NA-disappearance, but their similar enhancing effect on SIF challenges the assumption of a primary importance of central NA-system in this behavior. By contrast, the increase in jumping behavior recorded additionally to SIF, seems to be a great extent dependent on NA-uptake inhibiting properties of tested drugs.

Aggression↗
PubMed1982

The effects of acute and repeated treatment with salbutamol, a beta-adrenoceptor agonist, on clonidine-induced hypoactivity in rats.

A dose-dependent decrease in exploratory activity of naive rats was observed after 5-20 mg/kg i.p. of salbutamol. This effect was antagonized by the pretreatment with propranolol and yohimbine. Furthermore, in a single dose of mg/kg salbutamol increased clonidine-induced hypoactivity. By contrast to acute effects, repetitive administration of salbutamol (5 mg/kg twice daily for 10 days) failed to change exploratory activity of rats and abolished the clonidine-induced hypoactivity. The results demonstrate differences in the acute and chronic effects of salbutamol on behaviour which may indicate changes in the sensitivity of adrenergic pre- as well as postsynaptic alpha-adrenoceptors. Tentatively, the results could be explained by development of alpha2-adrenoceptor subsensitivity and the involvement of beta-adrenoceptors in the regulation of their activity.

Albuterol↗
PubMed1982

Different pharmacokinetic and pharmacological effects following acute and chronic treatment with imipramine.

Two schedules of imipramine (IM) administration were compared, a single intraperitoneal dose (10 mg/kg) (I) and chronic oral dosage (10 mg/kg twice a day for 14 days) (II). During schedule I, IMI reached maximal concentration in brain twice as high as that of its metabolite, desipramine (DMI), but disappeared more rapidly. During schedule II, DMI achieved concentrations twice as high as those of IMI which were maintained in a long-lasting plateau and there were considerable differences in areas of brain concentration curves. During schedule I, depletion of brain noradrenaline (NA) induced by H77/77 and of 5-hydroxytryptamine (5-HT) by p-chloro-amphetamine, were inhibited. During schedule II, after DMI concentration had become high and that of IMI low, only NA depletion but not that of 5-HT, was inhibited. At the same time, fenfluramine-induced hyperthermia was not antagonized although it was inhibited in schedule I. These findings may be relevant to those obtained clinically and may help to shed light on mechanisms of antidepressant action.

Animals↗
PubMed1981

Rapid-eye-movement sleep deprivation inhibits clonidine-induced sedation in rats.

The effects of 24 and 48 h of rapid-eye-movement sleep deprivation (REMD) on clonidine-induced sedation and [3H]clonidine binding to cortical membranes were studied in rats. REMD did not affect the exploratory behaviour (ambulation, rearing + peeping) of normal rats. The sedative effect of clonidine (0.2 mg/kg s.c.) on the rearing + peeping behaviour of rats was inhibited by REMD. [3H]Clonidine binding in the cerebral frontal cortex remained unaffected. The results are discussed in terms of changes in the noradrenergic system.

Animals↗
PubMed1981

Chronic treatment with some atypical antidepressants increases the brain level of 3-methoxy-4-hydroxyphenylglycol (MHPG) in rats.

We examined the effects of some atypical antidepressants with central antiserotonergic activity (mianserin, trazodone, danitracen, pizotifen), and 5-HT receptor blocking agents (cyproheptadine and metergoline), on whole rat brain levels of the main noradrenaline (NA) metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG). In acute experiments, when drugs were injected in a single dose 1, 2, 4, 24 or 48 h before decapitation, only mianserin elevated the MHPG level. In chronic experiments (drugs given b. i. d. for 3 weeks, the last dose being given 4 or 48 h before decapitation), all the drugs significantly increased the concentration of whole brain MHPG. The results indicate that chronic administration of atypical antidepressants leads to activation of the central NA system. It seems, with the exception of mianserin, that this is a secondary phenomenon, resulting from the antiserotonergic activity of the drugs. Our results further corroborate the existence of a serotonergic-noradrenergic interaction, consisting of an inhibitory influence of serotonin on the noradrenergic system.

Animals↗
PubMed1981

Chronic treatment with antidepressants: protentiation of clonidine-induced aggression in mice via noradrenergic mechanism.

The chronic (10 mg/kg i.p. twice daily, 10 days)-and not the acute-administration of amitriptyline, maprotiline or zimelidine enhances aggressiveness induced by clonidine in mice. An analogous potentiation of clonidine-induced aggressiveness was obtained with chronic administration (the schedule as above) of levomepromazine (2 mg/kg) or thioridazine (5 mg/kg) but not of spiperone (0.2 mg/kg). Fluoxetine (10 mg/kg), atropine (5 mg/kg), propranolol (10 mg/kg) or metergoline (0.5 mg/kg) given chronically (the schedule as above) also had no effect. The enhancement of clonidine aggressiveness induced by prolonged treatment with imipramine (10 mg/kg) was prevented by cycloheximide, an inhibitor of protein synthesis. The results supply further evidence for the previously proposed hypothesis that chronic administration of antidepressants enhances the responsiveness of central postsynaptic noradrenaline receptors.

Aggression↗
PubMed1981

Influence of salbutamol and other beta-agonists on hypothermia induced by clonidine, apomorphine and reserpine in mice.

Clonidine administered to mice induced hypothermia and this effect was antagonized by a single dose of the following beta-agonists: salbutamol, isoprenaline and terbutaline. The effect of these beta-agonists was completely antagonized by propranolol. The effect of terbutaline on reserpine-and apomorphine-induced hypothermia was also studied; it causing a slight but significant reversal of hypothermia. This effect was also blocked by propranolol. The results obtained here showed these beta-agonists behave in a manner similar to other antidepressant drugs. The data reinforces the view that beta-stimulation is of great importance in antidepressant action.

Albuterol↗