Biomedical subjects

O Pucilowski

Publications and source records attributed to O Pucilowski.

36 records · Page 2Linked to original sources

PubMed1992

Immobility-reducing effects of antidepressants in a genetic animal model of depression.

Chronic treatment with the tricyclic antidepressants imipramine (15 mg/kg) and desmethylimipramine (5 mg/kg) significantly reduced the exaggerated immobility normally exhibited by the Flinders Sensitive Line (FSL) rats in the Forced Swim Test. The control group, Flinders Resistant Line (FRL) rats were only slightly affected. In contrast, chronic treatment with the anticholinesterase diisopropyl fluorophosphate at doses known to down regulate muscarinic receptors did not alter swim test immobility in either FSL or FRL rats. Our findings support the validity of the FSL rats as an animal model of depression and suggest that serotonergic and/or noradrenergic, but not cholinergic mechanisms, may underlie the exaggerated immobility of the FSL rats.

Animals↗

PubMed1992

Ethanol and complement hemolytic activity of selectively bred hypercholinergic rats.

Depression and alcoholism are associated with impaired immune responses. Complement proteins and fragments participate in the induction and modulation of both specific and non-specific immune reactions. This study examined the effect of prolonged ethanol ingestion on complement CH50 levels in two strains of rats, the Flinders Resistant Line (FRL) and the Flinders Sensitive Line (FSL), that differ in cholinergic sensitivity and depressive tendencies. Chronic ethanol exposure given as either the source of drinking fluid or as a liquid diet had a significant inhibition on mean CH50 unit responses in both FSL (41-48%) and FRL (23-24%) rats. The difference in group response to ethanol was confirmed by a significant interaction of ethanol treatment versus group in the two-way ANOVA. The FSL rats appear to be more easily affected than FRLs. Genetic differences in the neurotransmitter systems, therefore, may play a role in susceptibility to immunosuppression resulting from ethanol exposure.

Alcoholism↗

PubMed1991

Chronic oral treatment with diltiazem or verapamil decreases isolation-induced activity impairment in elevated plus maze.

Adult male Wistar rats were either socially isolated or group-housed for 6 weeks and then tested in an elevated plus maze. During isolation the rats received either water or two concentrations of the calcium channel inhibitors, diltiazem or verapamil, in drinking solutions (approximately 5 and 10 mg/kg daily). Isolated rats showed a significantly lower total number of arm entries, a lower percentage of open arm entries and negligible time spent therein than did group-housed animals. Verapamil, in the higher dose, prevented that effect of isolation. Treatment with diltiazem brought about a similar tendency, though the effect did not reach statistical significance. Chronic treatment of group-housed rats with either drug failed to influence their behavior in the plus maze. We conclude that certain calcium channel inhibitors may decrease the behavioral deficit in the elevated plus maze that follows chronic social isolation.

Animals↗

PubMed1991

Diltiazem suppresses quinpirole-induced oral stereotypies in haloperidol withdrawn rats.

1. Tardive dyskinesia (TD) is one of the most serious untoward effects of chronic neuroleptic therapy. Dopaminergic receptor sensitization is assumed to be involved in its pathogenesis. 2. Male Wistar rats were administered (b.i.d.) intragastrically haloperidol (2 mg/kg), diltiazem (5 mg/kg), diltiazem plus haloperidol, and water (controls), for 21 days. 3. Forty eight hours after withdrawal the rats were injected ip with 0.3 mg/kg of quinpirole and observed for stereotypic behaviors (rearing, grooming, licking, and tongue protrusions). 4. There was a significant overall between-group difference in the duration of grooming and the number of tongue protrusions. The haloperidol withdrawn rats scored markedly higher than control and diltiazem alone treated rats. 5. Conjoint treatment with diltiazem and haloperidol prevented the increase of tongue protrusion episodes. 6. We conclude that concurrent diltiazem and haloperidol administration can prevent the occurrence of some behavioral manifestations of dopaminergic receptor supersensitivity, including a lingual dyskinesia.

Analysis of Variance↗

PubMed1991

Decreased hyperthermic effect of MK-801 in selectively bred hypercholinergic rats.

The Flinders Sensitive Line (FSL) of rats has been selectively bred to have increased sensitivity to cholinergic agonists. However, these rats exhibit altered responsiveness to a number of noncholinergic agents, such as apomorphine, buspirone and ethanol. This study compared the FSL and control Flinders Resistant Line (FRL) rats in terms of their hyperthermic response to the phencyclidine (PCP) receptor agonist, MK-801 (0.2 mg/kg SC) and their MK-801 binding characteristics. We have found that FSL rats react with a delayed hyperthermia, having a significantly lower hyperthermia for the first 120 min of observation. Thereafter the response does not differ in FSL and FRL rats. Both groups had similar affinities and numbers of [3H]MK-801 binding sites in the hippocampus/cerebral cortex. Pretreatment with scopolamine (1 mg/kg SC) failed to affect MK-801-induced hyperthermia in either line of rats. These findings suggest that selective breeding of FSL rats attenuated the secondary mechanisms involved in the PCP receptor-mediated hyperthermic response. However, by itself cholinergic supersensitivity does not appear to be a major factor in the blunted responsiveness of FSL rats to MK-801.

Animals↗

PubMed1991

Effects of calcium channel inhibitors on the hypothermic response to oxotremorine in normo and hypercholinergic rats.

The Flinders Sensitive Line of rats (FSL) has been selectively bred to have increased sensitivity to cholinergic drugs. Typically, these rats react with twice as great a hypothermic effect to muscarinic agonists such as oxotremorine, as do similarly bred Flinders Resistant Line rats (FRL). We compared the effects of three chemically different calcium channel inhibitors (diltiazem, nicardipine and verapamil) on the hypothermia induced in FRL and FSL rats by oxotremorine (0.2 mg kg-1 s.c.). Each drug was injected i.p. in a dose of 20 mumol kg-1 30 min before oxotremorine. Methylatropine (2 mg kg-1 s.c.) was administered 15 min before oxotremorine to block the peripheral effects of the agonist. The hypothermic effect of oxotremorine in FSL rats was antagonized by nicardipine and diltiazem. In contrast, verapamil failed to influence the hypothermic response in FSL rats. Verapamil significantly (P less than 0.05) augmented oxotremorine hypothermia in FRL rats. Diltiazem and nicardipine were without effect on oxotremorine-induced hypothermia in FRL rats. There were no significant changes in temperature in separate groups of FRL and FSL rats treated with calcium channel inhibitors alone.

Animals↗

PubMed1991

Nicardipine protects against chronic ethanol- or haloperidol-induced supersensitivity to apomorphine-induced aggression.

Affective apomorphine-induced aggression was induced in originally nonaggressive rats after withdrawal from prolonged ethanol or haloperidol treatment. If the animals were co-administered Ca(2+)-channel blockers like diltiazem or verapamil the aggressive response to apomorphine was markedly decreased. Nicardipine (2 and 5 mg/kg b.i.d.) significantly attenuated the aggression-enhancing effect of chronic ethanol or haloperidol withdrawal in nonaggressive rats. Chronic nicardipine, alone, did not enhance aggressive behavior in the nonaggressive rats. Acutely, it suppressed apomorphine-induced aggression but did not alter open field activity when injected into aggressive rats. These results demonstrate that a Ca(2+)-channel blocker of the dihydropyridine type can prevent the development of an ethanol or haloperidol-withdrawal supersensitivity to apomorphine-induced aggression. It attenuates the aggression-inducing effect of apomorphine without impairing general activity.

Aggression↗

PubMed1990

Effect of verapamil on submissive behavior in genetically bred hypercholinergic rats in a water competition test.

Male hypercholinergic FSL (Flinders Sensitive Line) and control FRL (Flinders Resistant Line) rats were placed on a water deprivation schedule and tested for dominance behavior with FSL/FRL pairs competing for water. FSL rats spent significantly less time drinking than their FRL partners. Acute injection of 10 mg/kg of verapamil, a calcium channel inhibitor, to FSL rats markedly increased their drinking time without influencing water intake in individually tested rats. This effect of the drug was no longer seen after prolonged 4 day treatment. It is suggested that submissiveness of FSL animals in the water competition test might be due to increased fear which is alleviated by verapamil treatment. Tolerance seems to develop to this effect of the drug.

Animals↗

PubMed1990

Antidepressant-like action of nicardipine, verapamil and hemicholinium-3 injected into the anterior hypothalamus in the rat forced swim test.

Male Wistar rats, chronically implanted with cannulas into the anterior hypothalamus, were acutely injected with the calcium channel inhibitors, diltiazem, nicardipine and verapamil, or the choline uptake blocker hemicholinium-3 and tested in the forced swim test. Hemicholinium-3, nicardipine and verapamil markedly increased the duration of active swimming. This antidepressant-like effect did not appear to reflect merely a hyperactive state as the drug-treated rats did not differ from vehicle-injected controls in their open field motility scores. Diltiazem failed to influence rats' performance in either test. Since nicardipine and verapamil, but not diltiazem, share choline uptake property with hemicholinium-3, it seems that this action plays a role in the antidepressant-like effect of all three drugs in the forced swim test.

Animals↗

PubMed1988

Diltiazem suppresses apomorphine-induced fighting and pro-aggressive effect of withdrawal from chronic ethanol or haloperidol in rats.

Dopaminergic receptor stimulation with apomorphine (5 mg/kg, i.p.) induced irritable aggression consisting of defensive upright postures, vocalization and biting attacks in pairs of responsive rats. Aggression was considerably decreased when the animals were pretreated with diltiazem, a Ca2+ channel inhibitor (5 or 10 mg/kg, i.p.). Originally non-responsive rats exhibited apomorphine-induced fighting upon withdrawal from prolonged ethanol (21 days, 3 g/kg, twice daily, intragastrically, i.g.) or haloperidol (14 days, 0.5 mg/kg, twice daily i.g.). If the animals were co-administered diltiazem i.g. 30 min prior to each dose of ethanol or haloperidol the aggressive response to apomorphine was significantly decreased; reduction in attack score being the most prominent. Chronic (14 or 21 days) diltiazem by itself did not facilitate the appearance of apomorphine-induced fighting in non-responsive rats. These results suggest that diltiazem can inhibit apomorphine-induced fighting and prevent the development of ethanol and haloperidol-induced behavioural supersensitivity to apomorphine.

Aggression↗

PubMed1987

Norepinephrine-mediated suppression of apomorphine-induced aggression and locomotor activity in the rat amygdala.

The effect of injections of norepinephrine (NE)-depleting toxin DSP-4 into the central amygdala (AMY) on apomorphine-induced fighting (AIF) was studied. In addition, the influence of such treatment on related parameters such as spontaneous activity, pain sensitivity and changes in locomotion after (+)3-PPP or apomorphine (1 mg/kg SC each) were verified. Finally, injections of NE or phenylephrine into the AMY five min before AIF were performed. DSP-4 induced marked (-71%) and selective fall in NE within the AMY accompanied by significant increase in aggressive response to 5 mg/kg of apomorphine. DSP-4-treated animals were less active in the open field and more sensitive to pain in a hot plate test. They were also more responsive to locomotor-augmenting action of apomorphine. Significant suppression of AIF was seen after injections of NE and phenylephrine into the AMY. The results suggest that NE input to the AMY plays an inhibitory role in dopamine-related locomotion and aggressivity. Moreover, amygdalar NE appears to be involved in general activity and pain perception modulation.

Aggression↗

PubMed1987

Chronic treatment with antidepressant drugs and ECT differentially modifies the hypothermic action of clonidine and guanfacine.

The hypothermia inducing action of clonidine and guanfacine was abolished by yohimbine and idazoxan pretreatment which suggests an alpha 2-adrenoceptor involvement in this effect. The effects of acute and chronic treatment with the antidepressant drugs desipramine (DMI), amitriptyline (AMI), maprotiline (MAP), mianserin (MIAN), iprindol (IPR), alaproclate (ALA) and electroconvulsive treatment (ECT) on the hypothermic action of the alpha 2-adrenoceptor agonists clonidine and guanfacine were studied. Acute administration of MIAN potentiated clonidine induced hypothermia whereas acute MIAN, IPR and ALA potentiated guanfacine induced hypothermia. Repetitive DMI, AMI and MAP treatment attenuated clonidine-induced hypothermia whereas guanfacine-induced hypothermia was potentiated by chronic treatment with DMI, AMI, MAP and MIAN, ECT applied without anaesthesia attenuated both clonidine and guanfacine hypothermia, however, under ethyl ether anaesthesia ECT was effective only towards guanfacine hypothermia. This discrepancy is discussed in terms of the relative selectivity of the agonists used, the reliability of agonist studies for indexing receptor function, and possible pharmacokinetic interaction.

Animals↗

PubMed1986

Chemical lesions of the nucleus accumbens septi in rats: effects on muricide and apomorphine-induced aggression.

To assess the influence of monoaminergic neurones in the nucleus accumbens septi (NAS) on muricidal and apomorphine-induced aggression, bilateral intraaccumbens injections of relevant neurotoxins were performed. Neurochemical effects in the mesolimbic area (NAS and tuberculi olfactorii) and striatal tissue were investigated using high performance liquid chromatography. 6-Hydroxydopamine (6-OHDA) with desipramine pretreatment significantly decreased mesolimbic dopamine (DA) metabolism, 5,7-dihydroxytryptamine (5,7-DHT) plus desipramine diminished serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), while DSP-4 depleted noradrenaline (NA), 5-HT, 5-HIAA and tryptophan in the mesolimbic area. No significant biochemical changes were observed in the striatum. Behaviourally, 6-OHDA-treated rats were markedly more aggressive in the apomorphine-induced fighting test. Similarly, DSP-4 injections into the NAS (10 micrograms/1 microliter) enhanced this type of aggression. The 5,7-DHT lesion did not alter apomorphine-induced fighting. None of the neurotoxins induced muricidal behaviour. It is concluded that dopaminergic postsynaptic receptors in the NAS may be involved in the pro-aggressive effect of apomorphine. The results support the hypothesis that NA-containing neurones play an inhibitory role in apomorphine-induced aggression and suggest that such a DA-NA interaction might occur in the NAS.

5,7-Dihydroxytryptamine↗

PubMed1983

Aggressive behaviour and the central serotonergic systems.

A brief critical review of serotonin involvement in two classes of aggressive behaviour, i.e. affective and predatory aggression, is presented. Special emphasis is put on the differentiation between the role played in aggression by the two ascending serotonergic systems, the mesolimbic and the mesostriatal. It is concluded that only serotonergic neurons from the dorsal raphe nucleus forming the mesostriatal system play an inhibitory role in both classes of aggression. The mesolimbic system does not seem to be directly involved in an aggression modulation. The data suggesting that the dorsal raphe may mediate its inhibitory influence through the medial amygdala is presented and discussed. Finally some attention is given to the problem of serotonin metabolism variability (biorhythm) and its implications in behavioural studies.

Affect↗

PubMed1981

Lesion of serotonergic neurons antagonizes clonidine induced suppression of avoidance behavior and locomotor activity in rats.

The effects of clonidine on avoidance acquisition and locomotor activity were studied in male Wistar rats with 5,6-dihydroxytryptamine (5,6-DHT) lesions of the median raphe nucleus. Lesioned animals showed marked depletion in forebrain serotonin and 5-hydroxyindole acetic acid concentrations. clonidine (0.2 mg/kg IP in a single daily dose for 6 consecutive days) inhibited avoidance acquisition and reduced locomotor activity in unlesioned rats. In 5,6-DHT rats clonidine failed to produce depressive effect. The resistance of raphe-lesioned rats to clonidine is discussed on the basis of possible interaction between noradrenergic and serotonergic brain systems.

5,6-Dihydroxytryptamine↗

PubMedDate not supplied

Different effect of diltiazem and nifedipine on some central actions of ethanol in the rat.

The effect of two Ca2+ channel inhibitors (CCIs) on ethanol-induced hypothermia and hypnosis, on tolerance formation to both effects, and on audiogenic convulsions during ethanol withdrawal was studied in rats. Nifedipine, 2 and 5 mg/kg IP, significantly augmented the hypnotic action of ethanol without affecting hypothermia. Diltiazem failed to influence either effect of the toxin. Rectal temperature did not change in ethanol-naive rats after acute injection of diltiazem or nifedipine. Both drugs dose-dependently suppressed the development of tolerance to the hypothermic effect of ethanol without affecting the tolerance to the hypnotic action. Only nifedipine markedly suppressed the audiogenic seizure response in ethanol withdrawn animals. These data suggest that Ca2+ channels play a role in both acute and chronic effects of ethanol while pointing to certain differences in behavioral effects of various CCIs.

Acoustic Stimulation↗

PubMedDate not supplied

Enhanced affective aggression in genetically bred hypercholinergic rats.

Affective aggression was studied in pairs of Flinders Sensitive Line hypercholinergic rats (FSL) and Flinders Resistant Line (FRL) rats in shock-induced and apomorphine-induced fighting tests. FSL rats were significantly more aggressive in both tests. They had higher pain threshold, assessed by the jump-flinch method, than FRL rats. It is concluded that genetically developed cholinergic system supersensitivity has resulted in enhanced responsiveness to stimuli eliciting affective aggression.

Acetylcholine↗

PubMedDate not supplied

Effect of chronic clonidine treatment and lesion of the locus coeruleus on the conditioned avoidance behavior in rats.

The effect of chronic clonidine treatment (0.2 mg/kg ip. during 10 consecutive days) on two-way avoidance acquisition was investigated in two groups of rats; sham operated and bilaterally lesioned with the locus coeruleus. Clonidine almost completely blocked the acquisition of avoidance reaction in both groups. In rats injected with saline, lesion of the locus coeruleus significantly decreased the avoidance reaction. The results indicate that destruction of presynaptic sites of clonidine action in neurons of the locus coeruleus failed to change the action of drug.

Animals↗