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V Klimek

Publications and source records attributed to V Klimek.

At least 37 records · Page 2Linked to original sources
PubMed1993

MK-801-induced symptoms of sensitization. The lack of correlation with the extracellular concentration of dopamine in the rat prefrontal cortex.

It was found that MK-801 evoked signs of behavioral sensitization to its own behavioral effects. A second injection of MK-801 (0.4 mg/kg) given 24 h after the first one (also 0.4 mg/kg) evoked stronger behavioral effects than the first dose. MK-801 (0.4 mg/kg) enhanced the extracellular concentration of dopamine (DA) in the prefrontal cortex (PFC). A second dose of MK-801 (0.4 mg/kg) given 24 h after the first one, evoked a quantitatively similar effect on the extracellular concentration of DA. The above results indicate that, at least in the PFC, the enhanced behavioral responsiveness to subsequent doses of MK-801 is not correlated with alterations in the extracellular concentration of DA.

Animals↗
PubMed1993

MK-801 elevates the extracellular concentration of dopamine in the rat prefrontal cortex and increases the density of striatal dopamine D1 receptors.

In the present study we found that MK-801 (dizocilpine), given peripherally in doses (0.2 and 0.4 mg/kg) which evoked locomotor activation in rats, enhanced in a dose-dependent manner the extracellular concentration of dopamine (DA) in the rat prefrontal cortex (PFC). MK-801 used in similar range of doses (0.2, 0.4 mg/kg) failed to alter the DA content in superfusates of the rat striatum (STR). It was also found that single doses of MK-801 enhanced the density of D1 receptors, assessed by the [3H]SCH 23390 binding in the rat STR, but not in the limbic forebrain. An increase in the density of D1 receptors was observed at 24, but not 2, h after MK-801 administration. MK-801 failed to alter the density of D2 receptors in the STR and limbic forebrain. The available data indicate that MK-801 may enhance the dopaminergic neurotransmission by at least two separate mechanisms: a fast one, associated with the release of DA in PFC, and a slow one, resulting from the increase in the D1 receptor density.

Animals↗
PubMed1993

Strain differences in clonidine-induced aggressiveness in mice and its interaction with the dopamine system.

The influence of a genotype of inbred mice on the aggressive behavior induced by clonidine and the role of dopamine D1 and D2 receptors in that behavior were studied. Clonidine in a dose of 10 mg/kg evoked a strong aggressiveness in BALB/c, DBA/1, and CC57Br mice and an intermediate response in C57BL/6J, Albino Swiss, and CBA mice, whereas DD, A/He, and C3HA/y mice did not show any aggressive behavior. Apomorphine significantly potentiated the clonidine-induced aggressiveness in C57BL/6J mice. In Albino Swiss mice, SK&F38393 as well as quinpirole augmented the aggressive behavior evoked by clonidine. The clonidine-induced aggressiveness was blocked by SCH23390 and cis-flupentixol but not by (-)-sulpiride. In aggressive mice, the binding of [3H]SCH23390 was decreased in the limbic forebrain, whereas the binding of [3H]spiperone was not changed. The obtained results indicate that the potency of the clonidine-induced aggressiveness depends upon genotype of mice; moreover, the presence of a physiological function of D1 receptors is necessary for its occurrence.

Aggression↗
PubMed1991

The effect of (+)- and (-)-oxaprotiline administered repeatedly on the dopamine system.

The behavioural and biochemical effects of repeated (14 and 28 days) treatment with (+)-oxaprotiline (a noradrenaline uptake inhibitor) and (-)-oxaprotiline (levoprotiline, without influence on noradrenaline uptake; the clinically active antidepressant) were studied in rats. Both those enantiomers given repeatedly increased the locomotor and exploratory activity and reduced the immobility time in Porsolt's test. The D-amphetamine-induced locomotor hyperactivity, as well as the stereotypies induced by D-amphetamine and apomorphine, were increased by the oxaprotilines. Single-dose treatment with both the oxaprotilines was not effective in the tests mentioned above. Repeated (+)-oxaprotiline administration reduced the binding (Bmax but not KD) to dopamine D-1 receptors in the striatum and limbic system; levoprotiline was inactive. The binding to dopamine D-2 receptors was not changed by either drug. Both the enantiomers showed only low affinity for brain dopamine D-1 and D-2 receptors in vitro. The obtained results indicate that chronic treatment with (+)- and (-)-oxaprotiline increases behavioural responsiveness of the dopamine mesolimbic and striatal systems.

Animals↗
PubMed1990

The effect of repeated treatment with brofaromine, moclobemide and deprenyl on alpha 1-adrenergic and dopaminergic receptors in the rat brain.

The binding of [3H]prazosin to alpha 1-adrenoreceptors, as well as of [3H]SCH 23390 (R(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-o l) to dopamine D1 receptors, and [3H]spiperone to D2 receptors was studied following repeated administration of the monoamine oxidase inhibitors (MAOI) brofaromine, moclobemide and deprenyl to rats. Scatchard analysis showed no change in the density (Bmax) and affinity (Kd) of [3H]prazosin sites, yet the ability of phenylephrine (an alpha 1-adrenoceptor agonist) to compete for [3H]antagonist binding sites was enhanced in the cerebral cortex after repeated brofaromine administration, as well as in the hippocampus of rats pretreated with moclobemide and deprenyl. The density and the binding affinity of dopaminergic D1 and D2 receptors were not affected by repeated treatment with all the MAOI used. The results seem to indicate that a small increase in the alpha 1-adrenoceptor agonist affinity occurs after repeated administration of MAOI.

Animals↗
PubMed1990

Oxaprotiline enantiomers given repeatedly and brain alpha-adrenoceptors.

The influence of (+)- and (-)-oxaprotiline (OXA) given repeatedly on the behavioural effects mediated by alpha 1- and alpha 2-adrenoceptors as well as on the binding to brain alpha 1-adrenoceptors was studied. (+)-OXA given repeatedly for 14 days (but not 3 or 7 days) enhanced exploratory hyperactivity of rats induced by methoxamine injected intracerebroventricularly; (-)-OXA given for 3, but not 7 or 14 days, increased the methoxamine-induced exploration in rats. The locomotor hyperactivity induced in mice by d,1-threo-3,4-dihydroxyphenylserine was increased by repeated (14 days) (-)-OXA but not (+)-OXA. Neither OXA enantiomers given repeatedly modified the clonidine-induced locomotor hypoactivity in mice. Both enantiomers given repeatedly did not change the binding of [3H] prazosin to alpha 1-adrenoceptors (Bmax, KD) in the thalamus and hippocampus. Repeated (+)-OXA increased the affinity of alpha 1-adrenoceptors for phenylephrine in the cortex, thalamus and hippocampus. A similar effect of (-)-OXA was observed in the hippocampus only. The results indicate that both OXA enantiomers are able to enhance the responsiveness of brain alpha 1-adrenergic system, probably via the increase in the affinity of alpha 1-adrenoceptors for their agonists.

Animals↗
PubMed1990

[The effect of the deprivation of paradoxical sleep on the rotational and stereotyped behavior induced by selective agonists of the dopamine receptors].

The ability of selective D1 and D2 agonists of dopamine (DA) receptors SKE-38393 and Ly-171555 to induce rotational and stereotypes behaviour were studied in rats with unilateral striatal kainic acid lesion before and after procedure of REM sleep deprivation (REMSD) lasting for 5 days. It was found that REMSD SKF-38393 given along induced the ipsilateral rotation. REMSD increased the circling and decreased an oral stereotype simultaneously when SKF-38393 and Ly-171555 were given together. The depletion of brain DA in part with alpha-methyl-p-tyrosine (AMPT) in nondeprived rats fails to influence the rotational behaviour and stereotype when SKF 38393 was injected 30 min following Ly-171555. After REMSD the AMPT pretreatment prevents the rotational behaviour caused by Ly-171555 which restores SKF-38393. The results suggest that prolonged REMSD may induce nonidentical changes in the sensitivity of the postsynaptic D1 and D2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Repeated administration of antidepressants enhances agonist affinity for mesolimbic D2-receptors.

Studies have shown an increased responsiveness of the dopaminergic system after repeated administration of a variety of antidepressant drugs. In the present study, the effect of repeated administration (twice daily for 14 days) of imipramine and mianserin on the affinity of dopamine D2-receptors for quinpirole, a D2-agonist, and on the quinpirole-induced locomotor hyperactivity was examined in rats. Repeated doses of imipramine and mianserin increased the affinity of quinpirole for [3H]spiperone binding sites in membranes prepared from the limbic system but not the striatum. The locomotor hyperactivity induced by quinpirole was enhanced by chronic treatment with both antidepressants. The data indicate that the enhanced responsiveness of the dopaminergic system in rats, observed after chronic treatment with antidepressants, may result from an increased affinity of agonists at D2-receptors in the mesolimbic system.

Animals↗
PubMed1989

[Clopheline-induced aggression in mice: role of genotype and the dopaminergic system].

Clophelin (CLO) in a dose 10 mg/kg induced aggressive behaviour in mice significantly dependent of genotype. Pretreatment with flupentixol and haloperidol inhibited or blocked CLO-evoked aggression in high-aggressive mice. Apomorphine administered with CLO enhanced aggression in low-aggressive mice. Stimulation of D2 receptors by bromocriptine failed to change CLO-induced aggression. It was suggested that dopamine system was involved in CLO-aggression through D1 receptors.

Aggression↗
PubMed1987

Desipramine given repeatedly enhances behavioural effects of dopamine and d-amphetamine injected into the nucleus accumbens.

The effect of desipramine (DMI) was studied after its repeated administration (10 mg/kg p.o., twice daily, 14 days) to rats, on the action of dopamine and d-amphetamine injected bilaterally into the nucleus accumbens. DMI, applied repeatedly but not acutely, prevented the sedative effect of dopamine and enhanced its stimulating action, as assessed by the open-field test. Repeated administration of DMI also enhanced d-amphetamine-induced locomotor hyperactivity. The number of [3H]SCH 23390 binding sites (D-1) in the limbic system decreased while the number of [3H] spiperone ones (D-2) remained unchanged. The results indicate that, like other antidepressant drugs studied earlier, DMI enhances neurotransmission in the dopamine mesolimbic system (nucleus accumbens) of the rat.

Animals↗
PubMed1987

Chronic treatment with antidepressants decreases the number of [3H]SCH 23390 binding sites in the rat striatum and limbic system.

Binding of [3H]SCH 23390 to dopamine D-1 receptors and of [3H]spiperone to D-2 sites was measured in identical membrane preparations of the striatum and limbic system of rats treated chronically (twice daily, for two weeks) with antidepressants. Chronic administration of imipramine, amitriptyline, mianserin, citalopram, bupropion, iprindole and electroconvulsive shocks, but not benztropine or cyproheptadine (non-antidepressants) decreased the number of [3H]SCH 23390 binding sites, while no change in the parameters of [3H]spiperone binding was observed. The serotonin2 receptor antagonist ketanserin when added to the incubation medium had no effect on [3H]SCH 23390 binding to D-1 sites. The results suggest that D-1 receptor subsensitivity is a component of the therapeutic effect of antidepressants.

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↗
PubMed1985

Antidepressant drugs given repeatedly increase binding to alpha 1-adrenoceptors in the rat cortex.

The effect of antidepressant drugs, administered repeatedly, on binding to alpha 1-adrenoceptors in the rat cerebral cortex was studied using [3H]prazosin as a ligand. Imipramine, amitriptyline, citalopram and mianserin increased the binding (Bmax) assessed at 8:00 h. At 20:00 h such an effect was produced by imipramine, citalopram and mianserin. [3H]Prazosin binding in control rats was higher at 20:00 h than at 8:00 h. An increase in the density of alpha 1-adrenoceptors may be associated with the therapeutic activity of antidepressant drugs.

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↗
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↗