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Biomedical subjects

W Danysz

Publications and source records attributed to W Danysz.

142 records · Page 8Linked to original sources
PubMed1983

Interaction between noradrenergic and serotonergic brain systems as evidenced by behavioral and biochemical effects of microinjections of adrenergic agonists and antagonists into the median raphe nucleus.

The effects of microinjections of adrenergic receptors agonists and antagonists into the median raphe nucleus (MR) on behavior and serotonin (5HT) metabolism was examined in rats. Administration of adrenergic alpha 1 and alpha 2 receptor agonists (noradrenaline, phenylephrine, clonidine) produced behavioral excitation in the open field test and a tendency to decrease the forebrain 5-hydroxyindolo-acetic acid (5HIAA) concentration. Opposite effects were seen after microinjection of adrenergic alpha receptor antagonists (phenoxybenzamine, phentolamine but not yohimbine). A significant negative correlation was found between the effects on locomotor activity and 5HIAA levels in these rats. No effect was present after injection of beta receptor agonist salbutamol or antagonist propranolol. It is suggested that noradrenaline released from noradrenergic terminals in the MR tonically inhibits the activity of 5HT neurons thus producing symptoms of 5HT deficiency and that this action of noradrenaline is probably limited to the effects on alpha 1 but not alpha 2 nor beta adrenoceptors in this brain region.

Adrenergic Agonists↗
PubMed1983

Behavioral studies in spontaneously hypertensive rats.

In the present study we examined some behavioral patterns in spontaneously hypertensive (SHR) male rats as compared with Wistar (W) rats. The following methods were employed: open field test, two-way active avoidance, passive avoidance, shock-induced fighting, shock-induced suppression of drinking (conflict test), and dominant-subordinate behavior in rats competing for water. Spontaneously hypertensive rats showed higher level of locomotor activity, lower emotionality, lower anxiety level, increased acquisition of avoidance tasks, and enhanced dominance behavior. In addition, hypertensive rats were less aggressive in shock-induced fighting test. It is concluded, that spontaneously hypertensive rats seem to be hyperactive in terms of locomotor activity while their emotionality appears to be paradoxically reduced.

Aggression↗
PubMed1983

The involvement of brain serotonin in the clonidine-induced hypothermia in rats.

The effects of manipulation with brain serotonergic (5HT) activity on clonidine-induced hypothermia in rats were investigated. Lesion to the median raphe nucleus as well as p-chlorophenylalanine pretreatment significantly potentiated the temperature decrease after 0.2 mg/kg of clonidine. Pretreatment with a 5HT releasing agent--fenfluramine, or a 5HT receptor agonist--m-chlorophenylpiperazine (mCPP) antagonized the effect of clonidine. Additionally, both fenfluramine and mCPP given alone produced an elevation in body temperature. These results are discussed in terms of an involvement of the 5HT neuronal system in clonidine hypothermia, and the dissociation of the role of 5HT system in clonidine-induced behavioral and vegetative effects is suggested.

Animals↗
PubMed1983

Some behavioral effects of microinjections of noradrenaline and serotonin into the hippocampus of the rat.

The effects of intra-hippocampal (dentate gyrus) microinjections of noradrenaline (NA) and serotonin (5HT) on various forms of rats' behavior were studied. NA injections produced an increase in the rats' exploratory behavior in the open field test, potentiated the animals' reaction to pain and significantly increased the aversive properties of an electric shock in the conflict test. 5HT injections inhibited the rats exploratory behavior in the open field test, attenuated the retention of a passive avoidance reaction and increased suppressant effects of shock in the conflict test. The findings indicate an antagonistic role of both monoamines in the regulation of various aspects of animal behavior and point to the hippocampus as a one of possible anatomic substrates for such an interaction.

Animals↗
PubMedDate not supplied

MIF-1 potentiates the action of tricyclic antidepressants in an animal model of depression.

In the present paper, the effect of simultaneous treatment of rats with low doses of MIF-1 and tricyclic antidepressants on rat behavior in the forced swim test was studied. It was found that MIF-1 stimulated in a dose-dependent manner "active" behavior of animals in this paradigm. The effect of MIF-1 appeared to be independent of changes in rats' locomotion in the open field test. The combined treatment of rats with MIF-1 (0.01 mg/kg IP) and amitriptyline (5 mg/kg IP) or desipramine (1.25 mg/kg) IP) significantly stimulated active behavior in the forced swim test above the level obtained with each of the drugs given separately. The present data suggest the potential clinical efficacy of a combined therapy of depressive patients with MIF-1 and small doses of tricyclic antidepressants.

Amitriptyline↗
PubMedDate not supplied

Effects of N-methyl-D-aspartate receptor antagonists on reinforced and nonreinforced responding for ethanol in rats.

Results of several recent studies indicate that the discriminative stimulus effects of ethanol are related, at least partially, to ethanol-induced decrease in the N-Methyl-D-aspartate (NMDA) receptor function. The role of NMDA receptors in ethanol reinforcement remains still unclear. The aim of the present study was to evaluate the effects of two novel NMDA receptor antagonists in rats lever pressing for 8% ethanol in the oral self-administration procedure. In addition, the effects of the drugs on intensity of nonreinforced responding for ethanol (i.e., "experimental craving") were examined in the extinction procedure. To assess selectivity of the drugs' actions the same range of doses was tested in rats lever pressing for water (control experiments). A low-affinity, uncompetitive NMDA receptor antagonist, MRZ 2/579 (2.5-7.5 mg/kg) selectively and dose-dependently decreased ethanol self-administration. This compound exerted also selective effects on nonreinforced responding for ethanol with lower dose (2.5 mg/kg) increasing and higher dose (5 mg/kg) suppressing operant behavior in the extinction procedure. MRZ 2/579 (5 mg/kg) did not alter open field activity when given in combination with either saline or ethanol (0.5-1 g/kg). In contrast, a glycineB site antagonist, MRZ 2/576 (2.5-7.5 mg/kg) did not produce any selective effects on either reinforced or nonreinforced lever pressing for ethanol. The present results suggest that MRZ 2/579 may selectively suppress both ethanol self-administration and experimental ethanol craving.

Animals↗
PubMedDate not supplied

[Sigma receptors: the key to therapeutic action or the side-effects of neuroleptics?].

The authors discuss psychotropic effects of phencyclidine (PCP) in the context of neurochemical mechanisms of schizophrenia. They concentrate on sigma receptors and PCP receptors and tie their activity with the dopaminergic system. The authors describe neuroleptic effects on sigma receptors and the therapeutic consequences. They include that the question whether the interaction of neuroleptics with sigma receptors results in therapeutic effects or rather in undesirable symptoms will decide about the future direction of treatment of schizophrenia.

Antipsychotic Agents↗
PubMedDate not supplied

Are ascending noradrenergic and serotonergic pathways necessary for effects of electroconvulsive treatment? Clonidine hypothermia and forced swim study.

Are ascending noradrenergic and serotonergic pathways necessary for effects of electroconvulsive treatment? Clonidine hypothermia and forced swim study. W. DANYSZ , W. KOSTOWSKI, M. HAUPTMANN, A. BIDZINSKI. Pol. J. Pharmacol. Pharm., 1989, 41, 15-22. Influence of chemical lesions to the noradrenergic locus coeruleus (intracerebral 6-OHDA injection, systemic administration of DSP-4) and serotonergic raphe system (intracerebral 5,7-DHT) on some effects produced by electroconvulsive shock (ECS) was studied. Administration of ECS slightly but significantly attenuated clonidine (CLO)-induced hypothermia and reduced rats immobility in forced swim test. DSP-4 reduced ECS action on CLO hypothermia remaining without effect upon ECS action in the second test. Other lesions were ineffective in both tests. This finding is in contrast to results obtained previously in animals receiving desipramine. The possible difference between ECS and antidepressant drugs action is discussed.

Animals↗
PubMedDate not supplied

The effect of microinjections of clonidine into the locus coeruleus on cortical EEG in rats.

Microinjections of clonidine into the locus coeruleus (LC) area synchronized rat cortical EEG. This effect of clonidine was attenuated by local pretreatment of rats with idazoxan, an alpha-2 adrenoceptor antagonist. The data indicate functional role of alpha-2 adrenoceptors within LC area in regulation of ceruleocortical activity, and point at the LC as one of brain targets for the sedative action of clonidine.

Animals↗
PubMedDate not supplied

Comparative studies on antidepressant action of alprazolam in different animal models.

Alprazolam, a new benzodiazepine from triazolobenzodiazepine group, produced anxiolytic action in the conflict test with potency similar to that of diazepam. The myorelaxant activity of the drug was relatively weak. Unlike desipramine, alprazolam failed to reduce the immobility of rats in the forced swim test and was unable to prevent clonidine-induced hypothermia. Alprazolam, unlike desipramine, failed also to potentiate behavioral effect of noradrenaline injected into the hippocampus. Alprazolam after acute but not chronic administration antagonized the synchronizing effect of clonidine on EEG pattern. On the other hand, alprazolam similarly to tricyclic antidepressants, prevented the suppression of dominance behavior by clonidine in rats competing for food. The results indicate that alprazolam acts only weakly upon noradrenergic mechanisms related to depression and to antidepressant action of drugs.

Alprazolam↗
PubMedDate not supplied

On the role of noradrenergic neurotransmission in the action of desipramine and amitriptyline in animal models of depression.

Three weeks of treatment with desipramine (DMI) and amitriptyline (AMI) reduced the hypothermic action of clonidine in rats. Both electrolytic and 6-hydroxydopamine lesions of the locus coeruleus (LC) and administration of DSP-4 counteracted the reduction of clonidine hypothermia produced by antidepressants. Lesions of the LC and DSP-4 administration also antagonized the anti-immobility action of single doses of DMI but failed to modulate the action of AMI in the forced swim test. Chronic DMI action on the rat immobility was reduced by 6-hydroxydopamine lesions of the LC: other lesions (electrolytic, DSP-4) were ineffective. Electrical stimulation of the LC increased the rat activity in the forced swim paradigm, producing an effect similar to that of antidepressants. The anti-immobility effect of DMI as well as LC stimulation were antagonized by drugs blocking alpha-adrenoceptors (phenoxybenzamine, prazosin) but not by propranolol, a non-selective antagonist of beta-adrenoceptors. On the other hand, the anti-immobility action of AMI was unchanged by all adrenolytics used in that study. The results indicate that the LC system and alpha 1-adrenoceptors play an important role in the antidepressive action of DMI, but not AMI, in the forced swim test.

Amitriptyline↗
PubMedDate not supplied

Mesolimbic noradrenaline but not dopamine is responsible for organization of rat behavior in the forced swim test and an anti-immobilizing effect of desipramine.

The role of mesolimbic monoaminergic innervation in the organization of rat behavior in the forced swim test (FST) and in the anti-immobilizing action of desipramine (DMI) in the test, was examined. The results can be summarized as follows: neither 6-hydroxydopamine (60HDA)-lesions nor electrical stimulation of the ventral tegmental area (A-10) and intra-accumbens dopamine (DA) microinjections produced specific (i.e. independent from changes in rats locomotion) effects on rat behavior or on DMI action in the FST. On the other hand, 60HDA lesions to the locus coeruleus (LC) antagonized the anti-immobilizing effect of DMI. It was also shown by us that the electrostimulation of the LC produced in the FST an effect similar to that of DMI. Moreover, the intra-accumbens injections of noradrenaline (NA) mimicked the effect of DMI in the test. Similar results were obtained after local administration of adrenergic receptor agonists--phenylephrine and isoproterenol. It is concluded that NA but not DA plays a crucial role in the organization of rat behavior in the FST and in the anti-immobilizing effect of DMI. The data suggest also a direct involvement of the nucleus accumbens septi in these neural processes.

Animals↗
PubMedDate not supplied

Evidence for the locus coeruleus involvement in desipramine action in animal models of depression.

Desipramine (DMI) effectively antagonized hypothermia induced by reserpine and clonidine in rats. DMI effects were attenuated or even abolished after electrolytic or 6-hydroxydopamine-induced lesion of the locus coeruleus (LC) as well as by administration of DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), a selective noradrenergic neurotoxin. Contrary to the LC lesions, electrolytic destruction of the ventral noradrenergic bundle did not change DMI action but antagonized reserpine-induced hypothermia by itself. Our results underline a possible involvement of the LC system in mechanism of antidepressive action, which was suggested previously in this laboratory.

Animals↗
PubMedDate not supplied

Studies on the locus coeruleus system in an animal model for antidepressive activity.

The present study was performed in order to evaluate the role of brain noradrenergic system of the locus coeruleus (LC) in mediating the effect of desipramine (DMI) in the behavioral despair (immobility) induced by forced swim in rats. Both single and repetitive doses of DMI significantly reduced the immobility. The effect of single dose of drug was reduced in LC lesioned rats. On the other hand, lesions failed to influence the action of repetitive doses of DMI. A lesion of the LC alone failed to influence animals' behavior in the immobility test. Electrical stimulation of the LC (either unilateral or bilateral) significantly reduced the immobility i.e. produced an effect similar to that produced by DMI. The possible involvement of the LC in action of DMI and mechanisms of depression is discussed.

Animals↗
PubMedDate not supplied

Concanavalin A increases N-methyl-D-aspartate-induced Ca2+ influx in cerebellar granule cells in culture.

Desensitization of glutamatergic receptors can be inhibited by various endogenous and/or exogenous agents e.g. by lectins. Effect of lectin, concanavalin A (con A) on N-methyl-D-aspartate (NMDA)-induced Ca2+ influx was studied in cultured cerebellar granule cells. Additionally the effect of con A on 3H-(+)-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate (3H-(+)MK-801) binding to NMDA receptors was investigated. Preincubation with con A enhanced NMDA efficacy (but not potency) to stimulate Ca2+ influx. The potency of MK-801 to inhibit NMDA effect was similar in both control and con A pretreated cells. Preincubation of cortical membranes with con A resulted in a robust decrease of Bmax 3H-MK-801 binding and modest decrease in affinity. This contradiction between Ca2+ influx and binding experiments may result from the difference in the subtype of NMDA receptors or different expression of con A action in both assays.

Animals↗