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Biomedical subjects

G Skuza

Publications and source records attributed to G Skuza.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

The effect of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, in the forced swimming test.

The present study examined the effects of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, in the forced swimming test in rats and mice. Administered in a single dose or three times both examined compounds reduced the immobility time in rats. Active doses used in that test either did not change the locomotor activity or decreased it. A similar effect in both tests was shown by active (R)-enantiomers CGP 40116 and CGP 43487. Reduction of the immobility time induced by CGP 37849 and CGP 39551 in the forced swimming test in rats was antagonized by haloperidol and (+/-)-sulpiride, but not by SCH 23390 or prazosin. CGP 37849, but not CGP 39551, also reduced the immobility time in the forced swimming test in mice. The results obtained indicate that CGP 37849 and CGP 39551 induce an antidepressant-like effect in the forced swimming test, probably via an indirect dopamine activation resulting from blockade of NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

The effects of combined treatment with MK-801 and antidepressant drugs in the forced swimming test in rats.

We found previously that combined administration of imipramine, citalopram and, to a lesser extent, mianserin with MK-801, a non-competitive NMDA receptor antagonist, reduced the immobility time in the forced swimming test in rats more potently than administration of the antidepressant or MK-801 alone. In present paper we examined the effect of other antidepressants in this model. (+)-Oxaprotiline and (-)-oxaprotiline which, when given alone, showed a weak positive effect, increased the action of MK-801. Fluoxetine, inactive when given alone, markedly increased the effect of MK-801. Moreover, the positive effect after combined treatment was found in the experiments in which antidepressants and MK-801 given separately were inactive. A reduction in the immobility time was also observed in those experimental paradigms in which the locomotor activity was not increased. The effects of combined treatment with the antidepressants studied + MK-801 were antagonized by haloperidol, but not by prazosin. The obtained results indicate that mainly a dopamine mechanism seems to be involved in the synergistic action of MK-801 and the antidepressants in the forced swimming test.

Animals↗
PubMedDate not supplied

Anxiolytic- and antidepressant-like effects of 7-OH-DPAT, preferential dopamine D3 receptor agonist, in rats.

The aim of the present study was to examine a potential anxiolytic- and antidepressant-like action of (+)-7-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (7-OH-DPAT), a preferential dopamine D(3) receptor agonist, and N-{4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl}-2-naphthylcarboxamide (BP 897), a partial dopamine D(3) receptor agonist, in male Wistar rats. Diazepam or imipramine were used as reference compounds. The anxiolytic-like effect of those drugs was tested in the elevated plus-maze test. The antidepressant-like effect was estimated using the forced swimming test. The obtained results showed that 7-OH-DPAT at low doses and BP 897 (like diazepam) induced anxiolytic-like effects in the elevated plus-maze test. 7-OH-DPAT, BP 897 and diazepam, tested at the doses effective in the model of anxiolytic-like actions, did not affect motor coordination. Moreover, 7-OH-DPAT at higher doses, like imipramine, showed antidepressant-like effect, significantly reducing immobility time in the forced swimming test. Combined treatment with 7-OH-DPAT and imipramine induced a stronger effect in Porsolt's test than administration of either drug alone, but did not increase the locomotor activity. In contrast, BP 897 was inactive in the forced swimming test when given alone but it potentiated the antidepressant-like effect of imipramine. These data suggest that preferential D(3) receptor agonists may play a role in the therapy of anxiety and/or depression, however, further studies are necessary to elucidate the mechanism of these actions.

Animals↗
PubMedDate not supplied

Central effects of Ro 19-6327 given acutely and repeatedly.

Some central effects of Ro 19-6327--a new MAO-B inhibitor--were studied in mice and rats. Given in low doses (1 or 3 mg/kg) Ro 19-6327 did not affect the locomotor activity of mice but its high dose (10 mg/kg) increased the activity. In rats Ro 19-6327 inhibited the locomotor activity but the effect was not dose dependent and not always significant. Ro 19-6327 did not change the locomotor activity in mice induced by L-DOPA (plus benserazide--an inhibitor of peripheral decarboxylase). The drug suppressed the reserpine-induced hypothermia and ptosis in mice and partly counteracted the apomorphine-induced hypothermia. It markedly enhanced (10 mg/kg) the amphetamine-induced stereotypy in rats. L-5-Hydroxytryptophan (L-5-HTP)-induced head twitch response was unchanged by Ro 19-6327. The drug given three times was inactive in forced swimming test. Repeated treatment with Ro 19-6327 (twice daily for 14 days) produced the enhancement of (+)-amphetamine- and nomifensine-induced hyperactivity in rats. Unlike a number of antidepressants, Ro 19-6327 did not potentiate the clonidine aggressiveness in mice, but--in contrast--inhibited it. The results suggest that Ro 19-6327 given repeatedly produces no changes in the responsiveness of the alpha-adrenergic system (in references to effects mediated by alpha 1-adrenoceptors). Adaptive changes in dopamine system are doubtful.

Animals↗
PubMedDate not supplied

Locomotor hyperactivity induced by MK-801 in rats.

The MK-801-induced hyperactivity in rats was antagonized by haloperidol and, to a lesser degree, by SCH 23390, a dopamine D-1 antagonist, and sulpiride, a dopamine D-2 antagonist. Combined treatment with MK-801 + D-amphetamine, or MK-801 + apomorphine caused a stronger locomotor hyperactivity than each of those drugs given alone. The stereotypy evoked by D-amphetamine or apomorphine was not changed by MK-801. Atropine potentiated the effect of MK-801. Prazosin, idazoxan or ritanserin did not affect the MK-801-induced hyperactivity. It was reduced by pretreatment with alpha-methyl-p-tyrosine (alpha-MT) and completely abolished by pretreatment with reserpine, or with reserpine+alpha-MT. Also combined administration of MK-801 + clonidine increased the activity of rats pretreated with reserpine+alpha-MT. Our results indicate that the dopamine system is mainly involved in the locomotor hyperactivity induced by MK-801.

Amphetamine↗
PubMedDate not supplied

Some central effects of opipramol given repeatedly.

Some central effects of opipramol administered repeatedly (twice daily, 14 days) were studied in rats and mice. Repeated or acute treatment with opipramol did not change the locomotor activity of rats. Given repeatedly, but not in a single dose, opipramol increased the (+)-amphetamine-induced hyperactivity. The (+)-amphetamine-induced stereotypy was unchanged by acute or repeated treatment with opipramol. The aggressiveness induced by clonidine in mice was attenuated by a single dose of opipramol, but it was markedly enhanced after repeated treatment with this drug. The immobility time of rats (behavioral despair test) was prolonged by a single dose of opipramol; when given three times, opipramol reduced the immobility time. The obtained results seem to indicate that repeated treatment with opipramol leads to similar effects in the experimental models as those after repeated treatment with typical antidepressant drugs, i.e. enhancement of the responses mediated by dopamine receptors (probably in the limbic system, but not in the striatum) and alpha 1-adrenoceptors in the brain.

Aggression↗
PubMedDate not supplied

The effect of repeated administration of imipramine, citalopram and mianserin on responsiveness of central serotonergic, alpha 2-adrenergic and cholinergic system in mice.

The effect of antidepressant drugs: imipramine, citalopram and mianserin given either in a single dose or twice a day for 14 days in a dose of 10 mg/kg was investigated in mice in tests for the responsiveness of central serotonergic (L-5 hydroxytryptophan-induced head twitches), alpha 2-adrenergic (donidine hypoactivity) and cholinergic (oxotremorine syndrome) systems. The effect of L-5 hydroxytryptophan was inhibited by repeated administration of citalopram and mianserin but unchanged by administration of imipramine. After a single administration only mianserin inhibited the L-5 hydroxytryptophan effect. Given repeatedly, the investigated antidepressant drugs did not affect the effect of clonidine; only mianserin potentiated the hypoactivity when given in a single dose. Repeatedly administered antidepressant drugs did not affect the action of oxotremorine, although imipramine (but not citalopram or mianserin) antagonized it after a single administration. The results indicate that under the present conditions repeatedly given mianserin and citalopram, but not imipramine, antagonize behavioral effects of L-5 hydroxytryptophan. No one of the investigated antidepressant drugs given repeatedly changed the responsiveness of alpha 2 -adrenergic and cholinergic systems to their agonists. It might be concluded that the changes in alpha 1-adrenergic and dopaminergic systems, observed previously after repeated administration of antidepressant drugs, are selective.

5-Hydroxytryptophan↗
PubMedDate not supplied

Antidepressant activities of WEB 1881, a new nootropic agent.

The central action, particularly potential antidepressant activity of WEB 1881, a new nootropic drug related to piracetam, was investigated in rats and mice. WEB 1881 antagonizes the reserpine- and apomorphine-induced hypothermia, potentiates the behavioral effect of DOPA and dihydroxyphenylserine, as well as the TRH-induced hyperthermia. Piracetam was only effective in the reserpine and DOPA tests. WEB 1881 is inactive in immobility test of Porsolt et al. It enhances the hind limb flexor reflex of the spinal rat, this effect being antagonized by prazosin and cyproheptadine. It exerts no effect on head twitches induced by L-5-hydroxytryptophan. The studied compound increases the noradrenaline and dopamine and turnover in the forebrain and brain stem. WEB 1881 given repeatedly potentiates the clonidine-induced aggressiveness and has no effect on the locomotor hyperactivity induced by D-amphetamine. The results indicate that in a number of tests WEB 1881 acts like other antidepressant drugs (but in others not), moreover, they suggest that this action is--at least partly--mediated by the central noradrenaline system.

Aggression↗
PubMedDate not supplied

Effect of antidepressant drugs and different receptor antagonists on the grooming induced by the dopamine D-1 agonist SKF 38393.

The effect of four antidepressant drugs: imipramine (IMI), amitriptyline (AMI), citalopram (CIT) and mianserin (MIA), as well as various receptor antagonists: prazosin (alpha 1), yohimbine (alpha 2), ritanserin (5-HT2), atropine (Ach), chlorpyramine (H1) and SCH 23,390 (D-1) on grooming potentiated by the selective D-1 receptor agonist SKF 38,393, as well as on spontaneous grooming was studied. Antidepressant drugs inhibited in a dose-dependent manner the SKF-38,393-induced grooming, as well as spontaneous grooming in rats and mice. A similar, dose-dependent inhibitory effect was shown by all the compounds mentioned above, which block various receptors. The results indicate that the inhibitory effect of antidepressants on the SKF 38,393-induced grooming is not specific.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMedDate not supplied

The influence of neuroleptics on the behavioural effect of 5-hydroxytryptophan.

The antagonism of neuroleptics of various groups (chlorpromazine, chlorprothixene, clopenthixol, clozapine, flupenthixol, fluphenazine, haloperidol, levomepromazine, mepazine, perazine, perphenazine, pimozide, prochlorperazine, promazine, spiperone, thiopromazine, thioridazine, trifluperazine, trifluperidol, triflupromazine) towards L-5-hydroxytryptophan (5-HTP) was assessed on the basis of inhibition of characteristic head-twitches. ED50 was assayed in mice and rats. The results indicate that all investigated neuroleptics inhibit the action of 5-HTP and their ED50 values are, as a rule, lower than the values of ED50 for catalepsy. That action is for the majority of neuroleptics more pronounced in mice than in rats. The present paper disucsses possible serotonergic, dopaminergic and also noradrenergic mechanism of action of neuroleptics in the 5-HTP test.

5-Hydroxytryptophan↗
PubMedDate not supplied

On the central antiserotonin action of trazodone.

Trazodone, an antidepressant drug with an unknown mechanism of action, has been examined in order to demonstrate its central antiserotonin action. Trazodone antagonizes the head twitch response induced by 5-hydroxytryptophan in rats and mice, or by-5-methoxytryptamine in rats (the ED50 values are 9.3, 5.2, and 10.8 mg/kg respectively). It counteracts convulsions induced by tryptamine in rats (ED50=3.75 mg/kg). Trazodone abolishes hyperthermia induced by serotoninomimetics (LSD, quipazine, fenfluramine) in rabbits. It does not affect ptosis induced by reserpine, and diminishes stimulation of the locomotor activity induced by amphetamine. Our findings demonstrate that trazodone has a central antiserotonin action, similarly as three other antidepressant drugs: mianserin, danitracen and doxepin, whose central antiserotonin action has been found previously.

Animals↗
PubMedDate not supplied

The effect of proadifen, a drug metabolism inhibitor, on action of imipramine and desipramine in mice.

Proadifen (SKF 524 A) inhibited the following effects of imipramine (IMI), without affecting those of desipramine (DMI) in mice: antagonism towards reserpine-induced hypothermia, ptosis and sedation, antagonism to apomorphine hypothermia and insignificant shortening of the immobility time in the behavioral despair test. Cerebral levels of DMI were very low after administration of IMI; pretreatment with proadifen did not affect the already low levels of DMI but significantly elevated these of IMI. This may indicate that some other than DMI metabolites (e.g., 2-hydroxy-derivatives) may be of importance for the action of IMI in mice in the tests employed in this study.

Animals↗
PubMedDate not supplied

Central effects of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, in mice.

Central effects of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, were studied in male Albino-Swiss mice. CGP 37849--at high doses only--increased the locomotor activity, while CGP 39551 decreased it. CGP 37849 and CGP 39551 did not change the locomotor activity, in monoamine-depleted mice (treated with reserpine + alpha-methyltyrosine). However, when administered together with clonidine, both those compounds produced a distinct hyperactivity. That antiakinetic effect was antagonized by haloperidol, but not by prazosin or idazoxan. In monoamine-depleted mice both the CGP compounds inhibited the locomotor hyperactivity evoked by apomorphine or L-DOPA (given jointly with benserazide). CGP 37849 antagonized the catalepsy evoked by fluphenazine, haloperidol, spiperone and reserpine. After CGP 39551 administration, a decreased muscle tension was observed, which rendered evaluation of the influence on catalepsy impossible. The obtained results (the antiakinetic effect, antagonized by haloperidol, and the anticataleptic effect) indicate that the NMDA receptor antagonists studied may act via an indirect activation of the dopamine system.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Central effects of repeated treatment with CGP 37849, a competitive NMDA receptor antagonist with potential antidepressant activity.

CGP 37849, a competitive NMDA receptor antagonist, was administered repeatedly (10 mg/kg po, twice daily for 14 days) to male Wistar rats. In behavioral studies it did not affect the locomotor activity, but enhanced the d-amphetamine-induced hyperactivity. Biochemical studies of the concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the rat cerebral cortex, striatum and nucleus accumbens showed that only the concentrations of DOPAC (an increase) and NA (a decrease) were changed in the nucleus accumbens. Repeated administration of CGP 37849 increased the density of dopamine D1 receptors labelled with [3H]-SCH 23390 in the rat striatum, but not in the limbic forebrain, having exerted no effect on the density of D2 receptors labelled with [3H]-spiperone. The density of alpha 1- and beta-adrenoceptors, labelled with [3H]-prazosin and [3H]-dihydroalprenolol, respectively, were unchanged in the cerebral cortex. The obtained results indicate that in some experimental paradigms CGP 37849 given repeatedly produces effects similar to those of typical antidepressant drugs.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Some central effects of kynurenic acid, 7-chlorokynurenic acid and 5,7- dichloro-kynurenic acid, glycine site antagonists.

Strychnine-insensitive glycine site is one of a few binding sites of NMDA receptor complex. The aim of these study was to find out whether compounds regarded as glycine antagonists-kynurenic acid (KA), 7-chlorokynurenic acid (7-CKA), 5,7-dichlorokynurenic acid (5,7-DCKA) evoke the effects analogous to those of the NMDA receptor antagonist, CGP 37849 (or MK-801) and/or can modulate the effects of the last compounds in rats. KA (but not 7-CKA, given ip) inhibited electroshock-induced seizures and increased the anticonvulsant effect of CGP 37849. CGP 37849-induced locomotor hyperactivity was enhanced by KA, 7-CKA (icv but not ip) and 5,7-DCKA. D-Amphetamine-induced hyperactivity was inhibited by KA as well as 7-CKA. In monoamine-depleted rats 7-CKA (but not KA) increased the antiakinetic effect of clonidine; the antiakinetic effect of L-DOPA was enhanced by 7-CKA and 5,7-DCKA, but not by KA. KA and 7-CKA did not change the spiperone-induced catalepsy but they attenuated the anticataleptic effect of CGP 37849; the studied drugs did not change the anticataleptic effect of MK-801. 7-CKA given icv did not influence the spiperone-induced catalepsy as well as the anticataleptic effect of CGP 37849. In the forced swimming test KA, given once, prolonged (50 mg/kg) or did not change (200 and 300 mg/kg) the immobility time. 7-CKA did not affect the immobility time in this model. When given three times KA (200 mg/kg) and 7-CKA (20 mg/kg) reduced the immobility time; the lower doses of KA and 7-CKA prolonged or did not change the immobility time, respectively. Joint injection with imipramine and KA (or 7-CKA) induced the decrease of immobility time (vs imipramine alone or glycine antagonist alone); in the case of joint injection with citalopram + KA (or 7-CKA), the time of immobility was prolonged or not changed. In conclusion, the obtained results point to similarities between glycine antagonists (kynurenine derivatives) and CGP 37849 and to the possibility of positive cooperation between the NMDA- and glycine-sites antagonists.

Amphetamine↗
PubMedDate not supplied

Some behavioral effects of CNQX AND NBQX, AMPA receptor antagonists.

CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline), two competitive AMPA (non-NMDA glutamate) receptor antagonists, as well as their interaction with CGP 37849, a competitive NMDA receptor antagonist, were studied in rats and mice. CNQX and NBQX inhibited the locomotor activity of naive rats. No symptoms of behavioral excitation were observed. CGP 37849 induced locomotor hyperactivity which was reduced by CNQX and NBQX. In monoamine-depleted rats (pretreated with reserpine + alpha-methyl-p-tyrosine), none of the two quinoxalines nor CGP 37849 antagonized akinesia. The antiakinetic effect of L-DOPA was increased by CGP 37849, but not by CNQX or NBQX. The latter action of CGP 37849 was decreased by CNQX and NBQX. The antiakinetic effect of clonidine was not changed by CNQX. The locomotor hyperactivity induced by apomorphine or cocaine was not modified by CNQX. Neither of the quinoxalines changed the catalepsy induced by haloperidol or spiperone. The fluphenazine catalepsy was slightly decreased by CNQX and increased by NBQX. CNQX and NBQX were inactive in the forced swimming test; CNQX (but not NBQX) increased the CGP 37849-induced reduction of the immobility time. CNQX decreased the muscle tone of hind limbs in naive and monoamine-depleted rats. The obtained results indicate that the AMPA receptor antagonists differ in their neuropharmacological profile from CGP 37849, an NMDA receptor antagonist. There is no positive cooperation (except for the forced swimming test) between NMDA and AMPA receptor antagonists; on the contrary, an antagonistic between them has been observed.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMedDate not supplied

Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.

GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] has been described as a non-competitive AMPA (non-NMDA glutamate) receptor antagonist. In the present paper some behavioral effects of GYKI 52466 were studied in male Wistar rats and male Albino Swiss mice. GYKI 52466 reduced the locomotor activity in normal rats and mice, without evoking any symptoms of behavioral stimulation. The CGP 37849-induced hyperlocomotion was increased by GYKI 52466. The akinesia in monoamine-depleted rats was not affected by the drug studied. The antiakinetic effect of L-DOPA was not changed by GYKI 52466, whereas the antiakinetic effect of L-DOPA+CGP 37849 was decreased. GYKI 52466 increased the hyperlocomotion induced by apomorphine or cocaine. The drug did not change the catalepsy induced by haloperidol or fluphenazine, as well as the anticataleptic effect of CGP 37849. GYKI 52466 was inactive in the forced swimming test, but increased the antidepressant effect of CGP 37849. The flexor and extensor muscle tone of the rats hind limb was not modified by GYKI 52466. The results obtained indicate that GYKI 52466 shows a neuropharmacological profile similar but not identical with that of the quinoxalines (competitive AMPA receptor antagonists) studied previously.

Animals↗