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G Skuza

Publications and source records attributed to G Skuza.

At least 19 recordsLinked to original sources
PubMed2002

Effect of repeated treatment with tianeptine and fluoxetine on central dopamine D(2) /D(3) receptors.

Tianeptine (TIA) is an antidepressant drug that has been shown to decrease extracellular serotonin level and reveals no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced any adaptive changes in the central dopamine D(2)/D(3) system (behavioural and biochemical) similar to those reported earlier for tricyclic antidepressants. Experiments were carried out on male Wistar rats. TIA was administered at a dose of 5 and 10 mg/kg once or repeatedly (twice daily for 14 days). Fluoxetine (FLU), used as a reference compound, was also administered at a dose of 10 mg/kg. The results obtained showed that TIA or FLU administered repeatedly increased the hyperlocomotion induced by D-amphetamine and 7-hydroxy-dipropylaminotetralin (7-OH-DPAT). Biochemical study revealed a decrease in the [(3)H]7-OH-DPAT binding sites after acute and repeated treatment with TIA or FLU in the islands of Calleja minor, as well as in the shell part of nucleus accumbens septi. On the other hand, both TIA and FLU administered repeatedly increased the binding of [(3)H]quinpirole (a D(2)/D(3) receptor agonist) in the nucleus caudatus as well as in the core part of the nucleus accumbens septi. Similar effects have been observed when dopamine D(2)/D(3) receptors were visualized with the use of [3H]raclopride, a dopamine D(2)/D(3) receptor antagonist. However, TIA and FLU induced a decrease in the level of mRNA encoding for dopamine D(2) receptors, not only after repeated but also after acute treatment. These results indicate that repeated TIA and FLU administration induces adaptive changes in the dopaminergic D(2)/D(3) system and especially enhances the functional responsiveness of dopamine D(2) and D(3) receptors. However, the question of whether this increased responsiveness is important for clinical antidepressant efficacy remains open.

Animals↗
PubMed2002

A potential antidepressant activity of SA4503, a selective sigma 1 receptor agonist.

The aim of the present study was to examine SA4503 [1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride], a novel selective receptor agonist, in respect of its potential antidepressant action. To this end we used a forced swimming test in rats to study SA4503 alone, as well as its interaction with imipramine, a classic tricyclic antidepressant. SA4503 decreased the immobility time in the forced swimming test in rats (although only at one of the three doses used); at the same time it did not change the locomotor activity recorded under the same experimental conditions. Moreover, SA4503 showed a synergistic effect with imipramine in the forced swimming test (both those compounds given jointly decreased the immobility time, but were ineffective when administered separately). It had previously been shown that repeated administration of antidepressants with different pharmacological profiles enhanced the action of D-amphetamine, quinpirole and other dopamine stimulants. SA4503 administered repeatedly increased the locomotor hyperactivity induced by D-amphetamine and quinpirole (a dopamine D /D receptor agonist), but not by (+/-)-7-hydroxy-dipropyloamino-tetralin hydrobromide [(+/-)-7-OH-DPAT; a dopamine D receptor agonist]. The results presented in this paper support the suggestion that SA4503 may have potential antidepressive properties.

Animals↗
PubMed2001

Effect of repeated treatment with tianeptine and fluoxetine on the central alpha(1)-adrenergic system.

Tianeptine (TIA) is an antidepressant drug which enhances the reuptake of serotonin but, in contrast to tricyclics, shows no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced adaptive changes in the alpha(1)-adrenergic system, similar to those reported by us earlier for tricyclic antidepressants. The experiments were carried out on male mice and rats. TIA was administered at a dose of 5 or 10mg/kg once or repeatedly (twice daily for 14 days) and fluoxetine (FLU), used as a reference compound, at a dose of 10mg/kg. The obtained results showed that TIA administered repeatedly potentiated the methoxamine- and phenylephrine (PHEN)-induced exploratory hyperactivity in rats and clonidine-induced aggressiveness in mice, the effects mediated by alpha(1)-adrenoceptors. TIA given repeatedly (but not acutely) increased the binding (B(max)) of alpha(1)-adrenergic receptors in cerebral cortex for [(3)H]prazosin. However, the ability of the alpha(1)-adrenoceptor agonist PHEN to compete for these sites was not significantly changed. The above results indicate that repeated TIA administration increases the responsiveness of the alpha(1)-adrenergic system (behavioural and biochemical changes). On the other hand, FLU did not affect any behavioural and biochemical changes in this system.

Adrenergic alpha-Agonists↗
PubMed1999

The anticataleptic effect of 7-OH-DPAT: are dopamine D3 receptors involved?

The paper examined the effect of 7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin), a dopamine D3 receptors-prefering agonist, on the catalepsy evoked by reserpine, haloperidol and fluphenazine in rats (male Wistar), as well as the influence of nafadotride, a dopamine D3 receptors-prefering antagonist, on that effect. The obtained results show that 7-OH-DPAT, as well as L-DOPA, a drug of choice in the therapy of Parkinson's disease, used for comparison, antagonize the catalepsy induced by reserpine, haloperidol and fluphenazine. Nafadotride, used in a dose (0.2 mg/kg) which inhibits the 7-OH-DPAT-evoked locomotor hyperactivity but does not affect the hypermotility induced by amphetamine and quinpirole, antagonizes the anticataleptic effect of 7-OH-DPAT or L-DOPA. It is therefore assumed that dopamine D3 receptors are involved in the anticataleptic effect of both 7-OH-DPAT and L-DOPA.

Animals↗
PubMed1998

Repeated trimipramine induces dopamine D2/D3 and alpha1-adrenergic up-regulation.

Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.

5-Hydroxytryptophan↗
PubMed1997

The behavioural effects of pramipexole, a novel dopamine receptor agonist.

Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydroc hlo ride) is a novel dopamine D2 family receptor agonist with a predominant action on D2 autoreceptors and with some D3 vs. D2 receptor preference. The central behavioural effects of pramipexole given subcutaneously to rats (male Wistar) and mice (Albino Swiss) are presented in this paper. Used in low doses (0.001-0.1 mg/kg), pramipexole induced locomotor hypoactivity which was antagonized by a low dose of spiperone; at higher doses (0.3, 1 mg/kg) it evoked hyperactivity which was inhibited by haloperidol, sulpiride and clozapine, but not by SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride). Pramipexole (0.1-1.0 mg/kg) antagonized the akinesia induced by combined pretreatment with reserpine (5 mg/kg) and alpha-methyl-p-tyrosine (250 mg/kg). Pramipexole (0.1-1 mg/kg) potentiated the hyperkinetic effect of L-DOPA (L-3,4-dihydroxyphenylalanine) (50 and 200 mg/kg, together with benserazide, 50 mg/kg) in naive and monoamine-depleted (reserpine + alpha-methyl-p-tyrosine) rats. The higher doses of pramipexole (1 and 3 mg/kg) evoked stereotypy which was antagonized by pretreatment with sulpiride or clozapine. The catalepsy induced by haloperidol, spiperone or fluphenazine was antagonized by pramipexole (1-3 mg/kg). Pramipexole (1 mg/kg) induced hypothermia in mice, which was antagonized by sulpiride. The obtained results indicate that pramipexole: (i) at low doses stimulates the dopamine D2 presynaptic autoreceptors; (ii) at higher doses stimulates dopamine D2 postsynaptic receptors. An effect on the dopamine D3 receptor cannot be excluded. At low doses pramipexole may have antipsychotic activity, and at higher ones antiparkinsonian activity.

Animals↗
PubMed1997

Antidepressant effects of pramipexole, a novel dopamine receptor agonist.

Pramipexole (2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrochl oride), a new dopamine receptor agonist with preference for D3 compared to D2 and D4 receptors, was tested in rats in respect of its potential antidepressant activity. In the forced swimming test the drug under study, given three times in rats, reduced the immobility time. In the forced swimming test, joint treatment with antidepressants (imipramine, amitriptyline) and pramipexole evoked a more potent effect than any of the drugs given alone; however, the locomotor hyperactivity was weaker after joint administration. Citalopram and fluoxetine, inactive per se in the forced swimming tests, visibly enhanced the antidepressant-like effect of pramipexole but, on the other hand, they attenuated the locomotor hyperactivity evoked by the drug. Repeated treatment with pramipexole (0.3 or 1 mg/kg, twice daily for 14 days) increased the locomotor activity measured at 1 h after the last dose. Repeated administration of pramipexole (as above) potentiated the D-amphetamine- or quinpirole-induced locomotor hyperactivity. The obtained results indicate that, in the tests used, pramipexole evokes effects similar to those of typical antidepressants and, at the same time, enhances their activity (the forced swimming test in rats); therefore it may be regarded as a potential antidepressant drug.

Animals↗
PubMed1997

Roxindole, a dopamine autoreceptor agonist with a potential antidepressant activity. II. Effects on the 5-hydroxytryptamine system.

Roxindole (ROX) (EMD 49980, 5-hydroxy-3-[4-(4-phenyl-1, 2,3,6-tetrahydropyridyl(1))-butyl(1)]-indole, mesylate), a potent selective agonist of presynaptic dopamine receptors with clinical antipsychotic and antidepressant activity, was studied pharmacologically in rats (male Wistar) and mice (male Albino Swiss) with respect to its influence on the central 5-hydroxytryptamine (5-HT) system. ROX did not induce the 5-HT1A syndrome (flat body and forepaw treading) in rats, but partly antagonized the syndrome evoked by 8-OH-DPAT. The 8-OH-DPAT-induced hypothermia in mice (a 5-HT1A effect) was not inhibited by ROX. The drug evoked hypothermia, which was antagonized by pindolol, but not by (+)-WAY-100135. ROX did not inhibit the m-chlorophenylpiperazine-induced hypothermia in mice (a 5-HT1B effect), or the exploratory hypoactivity in rats (a 5-HT1C effect). Head twitches induced by a low dose of L-5-HTP were potentiated by ROX, whereas those induced by its higher dose were antagonized. ROX also antagonized the hyperthermia induced by fenfluramine or trifluoromethylphenylpiperazine at a high ambient temperature in rats (a 5-HT2A effect). The results obtained indicate that ROX inhibits 5-HT uptake and shows 5-HT2A antagonistic and probably a 5-HT1B agonistic activities.

5-Hydroxytryptophan↗
PubMed1996

Neuropharmacological profile of EMD 57445, a sigma receptor ligand with potential antipsychotic activity.

EMD 57445 ((S)-(-)-[4-hydroxy-4-(3,4-benzodioxol-5-yl) -piperidin-1-ylmethyl]-3-(4-methoxyphenyl)-oxazolidin- 2-one) is a new sigma receptor ligand with only marginal affinity for many other (including dopamine) receptors. In the present study, central, particularly neuroleptic-like, effects of this compound were evaluated and compared with those of another sigma receptor ligand, rimcazole. EMD 57445 decreased locomotor activity in rats and mice. The amphetamine-induced locomotor hyperactivity and stereotypy were reduced by EMD 57445. The drug was able to inhibit the behavioural effects induced by apomorphine, i.e., the locomotor hyperactivity, stereotypy and aggression in rats, as well as climbing in mice. The hyperlocomotion induced by quinpirole (a dopamine D2/3 receptor agonist) and the grooming induced by SKF 38393 (a dopamine D1 receptor agonist) were decreased by EMD 57445. The behavioural stimulation evoked in rats by non-competitive (MK-801, (+)-5-methyl-10,11-dihydroxy-5H-dibenzo (a,b)-cyclohepten-5,10-imine hydrogen maleate) or competitive (CGP 37849, D,L-E-amino-4-methyl-5-phosphono-3-pentenoic acid) NMDA receptor antagonists was also inhibited. EMD 57445 decreased the cocaine-, morphine- or caffeine-induced locomotor hyperactivity in rats or mice. It neither induced catalepsy nor increased muscle tone in rats. Rimcazole had somewhat different effects: it increased the amphetamine stereotypy as well as the amphetamine-, quinpirole- and cocaine-induced locomotor hyperactivity in rats. The results indicate that EMD 57445 shows functional antidopaminergic activity and may be useful as an antipsychotic drug devoid of extrapyramidal side-effects.

Animals↗
PubMed1996

Antidepressant drugs given repeatedly change the binding of the dopamine D2 receptor agonist, [3H]N-0437, to dopamine D2 receptors in the rat brain.

The effects of antidepressants given in a single dose or repeatedly (10 mg/kg p.o., twice daily, 14 days) on binding to dopamine D2 receptors in the striatum and limbic forebrain of Wistar male rats were studied. [3H]N-0437, (2-(N[2,3(n)-3H]propyl-N-(2-thiofuranyl)-2'-ethylamino) -5-hydroxy-1,2,3,4-tetrahydronaphthalene), a dopamine D2 receptor agonist, was used as a ligand. Already a single dose of imipramine and fluoxetine caused a statistically significant decrease in the affinity of the ligand for dopamine D2 receptors in the striatum, but only at 72 h after drug administration. Also at 72 h after the single dose of mianserin a significant increase in the density of dopamine D2 receptors was observed. Repeated imipramine, amitriptyline and mianserin increased the affinity for dopamine D2 receptors in the striatum and in the limbic forebrain. Repeated fluoxetine increased that affinity in the striatum, but decreased it in the limbic forebrain. The density of dopamine D2 receptors was increased by the repeated administration of the antidepressants studied in the limbic forebrain, but was not changed in the striatum. The results obtained in the present study are in good agreement with the previously reported enhancement of behavioural responsiveness to dopamine and dopamine stimulants (dopamine D2 up-regulation) evoked by repeated treatment with antidepressants.

Amitriptyline↗
PubMed1996

Roxindole, a potential antidepressant. I. Effect on the dopamine system.

Roxindole (EMD 49980, 5-hydroxy-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl(1))-butyl(1)]-indole mesylate), a selective dopamine autoreceptor agonist and a potential antipsychotic drug, shows a clinical antidepressant efficacy. The present paper examined the neuropharmacological profile of roxindole in rats (male Wistar) and mice (male Albino Swiss) in respect of its influence on dopamine system. Used in low doses, roxindole decreased the locomotor activity, but in higher ones it did not induce a locomotor hyperactivity or stereotypy. It antagonized the amphetamine-induced hyperlocomotion, the amphetamine- or apomorphine-induced stereotypy, apomorphine climbing behaviour and reserpine-induced akinesia. The quinpirole-induced hyperlocomotion was inhibited by roxindole. When given alone, the drug in question, did not induce the catalepsy, but antagonized the catalepsy induced by haloperidol, spiperone and fluphenazine. The immobility time in the forced swimming test was reduced. Like typical antidepressants, roxindole given repeatedly (twice daily, 14 days) increased the hyperlocomotion induced by D-amphetamine. The results described above indicate that roxindole may have an antidepressant and antiparkinsonian activity and should be devoid of extrapyramidal side-effects.

Amphetamine↗
PubMed1996

The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist.

It was found previously that the MK-801 (an uncompetitive NMDA receptor antagonist)-induced locomotor hyperactivity in rats was potently increased by antidepressant drugs. The present paper analysed the locomotor hyperactivity induced by combined treatment with fluoxetine + MK-801 in male Wistar rats. The MK-801 hyperactivity was increased by citalopram (the latter effect was prevented by zacopride and ketanserin), sertraline, p-chloramphetamine, 8-OH-DPAT and TFMPP. The hyperlocomotion caused by fluoxetine + MK-801 was antagonized by tropisetron and zacopride and, to a lesser extent, by ketanserin, ritanserin and NAN-190, but not by WAY 100135, pindolol, metergoline or mianserin. Sulpiride and clozapine were able to inhibit the fluoxetine + MK-801 hyperlocomotion. The hyperlocomotion induced by D-amphetamine or apomorphine was not modified by fluoxetine or citalopram. Fluoxetine increased the release of dopamine (measured by a microdialysis method) in the striatum, induced by MK-801. The obtained results indicate that fluoxetine increases the MK-801-induced locomotor hyperactivity via activation of 5-HT3 receptors and, to a lesser degree, 5-HT2 ones.

Animals↗
PubMed1996

The effects of paroxetine given repeatedly on the 5-HT receptor subpopulations in the rat brain.

Effects of paroxetine (10 mg/kg PO, twice daily, 14 days) on 5-HT receptor subpopulations in the brain were evaluated pharmacologically, electrophysiologically and biochemically in male Wistar rats. Imipramine was used for comparison. Repeated paroxetine antagonized the 8-OH-DPAT-induced behavioural syndrome (a 5-HT1A effect); imipramine showed similar, yet weaker, activity. The 5-HT-or 8-OH-DPAT-induced inhibition of population spikes in hippocampal slices was increased by both those repeated antidepressants. Repeated (or acute) paroxetine decreased the density of and increased the affinity for 5-HT1A receptors ([3H]-8-OH-DPAT used as ligand) in the hippocampus, while imipramine induced opposite effects. m-Chlorophenyl piperazine (m-CPP)-evoked exploratory hypoactivity, a 5-HT2C effect, was reduced by repeated paroxetine, but not by imipramine. Either of the antidepressants given repeatedly antagonized TFMPP-induced hyperthermia (another putative 5-HT2C effect). 5-HTP-induced head twitches (a 5-HT2A effect) were inhibited by repeated paroxetine or imipramine. Either antidepressant given repeatedly decreased the density of 5-HT2A receptors ([3H]-ketanserin as a ligand) in the brain cortex, but did not change their affinity. The present results indicate that paroxetine given repeatedly induces secondary changes in 5-HT2 receptors, which lead to reduction of the 5-HT2 neurotransmission (reduced responsiveness of 5-HT2 postsynaptic receptors). The consequences of the secondary changes in 5-HT1A receptors, found here still await clarification.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Memantine, amantadine, and L-deprenyl potentiate the action of L-dopa in monoamine-depleted rats.

Some treatments used for Parkinson's disease attenuate locomotor depression in rats treated with reserpine and alpha-methyl-p-tyrosine. In the present study memantine (2.5, 5.0 mg/kg), amantadine (10, 20 mg/kg) (both uncompetitive NMDA antagonists), and L-deprenyl (1.0, 5.0 mg/kg; MAO-B inhibitor) were tested for possible synergistic interactions with the dopamine agonists: bromocriptine (2.5, 5.0 mg/kg) and L-dopa (50, 100 mg/kg, +benserazide, 100 mg/kg). At higher doses, memantine (10 mg/kg), amantadine (40 mg/kg), bromocriptine (5 and 10 mg/kg) and L-dopa (100, 200 mg/kg) but not L-deprenyl (up to 10 mg/kg) produced a pronounced increase in locomotor activity when given alone. The combination of memantine, amantadine and L-deprenyl with bromocriptine did not result in synergism of action and, at best, an additive effect was seen. On the other hand the combination of these agents with L-dopa produced a pronounced synergistic effect. Hence, the clinical observation that coadministration of L-dopa with either memantine or amantadine results in enhancement of their action is also reflected in an animal model of Parkinson's disease. Such a combination therapy should allow the use of lower doses of both drugs which may reduce the occurrence of side effects and may also be predicted to have additional benefits related to the neuroprotective properties of memantine, amantadine, and L-deprenyl.

Amantadine↗
PubMed1994

Pharmacological action of zotepine and other antipsychotics on central 5-hydroxytryptamine receptor subtypes.

The effect of the atypical neuroleptic zotepine (CAS 26615-21-4), in comparison with clozapine, risperidone and haloperidol, on the responsiveness of different 5-hydroxytryptamine (5-HT1) receptor subtypes to their agonists was examined in rats and mice. The above antipsychotics were investigated in the following behavioural tests: 8-OH-DPAT (8-hydroxy-dipropylaminotetralin)-induced behavioural syndrome in rats, mCPP (mchlorophenylpiperazine)-induced hypothermia in mice and mCPP-induced hypoactivity measured in the open field in rats. Zotepine, clozapine and haloperidol did not affect the behavioural syndrome induced by 8-OH-DPAT (the selective agonist of 5-HT1A, receptor), only risperidone (used in higher doses) attenuated the effect of 8-OH-DPAT. The mCPP-induced hypothermia in mice (a 5-HT1B effect) was affected by neither zotepine nor clozapine, risperidone and haloperidol, all of them used in low doses which did not influence per se the body temperature of mice. All the tested antipsychotics given at high doses induced hypothermia in control mice; at the same time, zotepine, clozapine and risperidone attenuated the hypothermic effect of mCPP. mCPP decreases the exploratory activity of rats, this effect being considered to be mediated by 5-HT1C receptors. The tested antipsychotics, used in low doses, influenced neither the exploratory activity nor the hypoactivity induced by mCPP. When used at higher doses, they induced hypoactivity in control rats; the hypoactivity after joint administration of zotepine, risperidone or haloperidol and mCPP was significantly greater than after mCPP alone, whereas clozapine slightly attenuated the effect of mCPP.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Some central effects of CGP 37849 and CGP 39551, the competitive NMDA receptor antagonists: potential antiparkinsonian activity.

Two new competitive NMDA receptor antagonists with oral activity CGP 37849 (D,L-E-amino-methyl-phosphono-3-pentenoic acid) and its ethyl ester CGP 39551 were studied in rats. CGP 37849 did not change the locomotor activity or increased it. The hyperactivity induced by CGP 37849 was antagonized by haloperidol but not idazoxan or prazosin. CGP 39551 decreased the locomotor activity. The studied compounds did not increase the locomotion in monoamine-depleted (pretreated with reserpine and alpha-methyl-p-tyrosine) rats. Clonidine induced antiakinetic effect in monoamine-depleted rats. This effect was more pronounced after joint administration of clonidine and CGP 37849 or CGP 39551. The locomotor hyperactivity induced by joint administration of CGP 37849 and clonidine was inhibited by haloperidol but not prazosin or idazoxan. CGP 37849 but not CGP 39551 also enhanced antiakinetic effect of L-DOPA (given together with benserazide) in monoamine-depleted rats. CGP 37849 antagonized the spiperone- and fluphenazine-induced catalepsy; CGP 39551 had considerably weaker antagonistic effect. The reserpine-induced catalepsy was attenuated by CGP 37849. MK-801, a non-competitive NMDA antagonist inhibited spiperone- but not reserpine-induced catalepsy. The obtained results indicate that CGP 37849 administered alone or in combination with L-DOPA or clonidine may be a potential antiparkinsonian drug.

2-Amino-5-phosphonovalerate↗
PubMed1992

The effect of antidepressant drugs on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist.

It was found earlier that imipramine, amitriptyline and citalopram enhanced the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist, in rats. Now, three other antidepressants: (+)-oxaprotiline, an inhibitor of the uptake of noradrenaline, (-)-oxaprotiline, an enantiomer devoid of any effect on the uptake of noradrenaline and fluoxetine, an inhibitor of the uptake of 5-hydroxytryptamine, have been examined in male Wistar rats. All those antidepressants, given in a single dose, increased the MK-801-induced locomotor hyperactivity. That increase was completely antagonized by haloperidol and partly by SCH 23390 and (+/-)-sulpiride; prazosin was inactive. Repeated administration of antidepressants produced a similar but more potent (than acute one) enhancement of the action of MK-801. Also, in that case haloperidol and SCH 23390 produced the strongest antagonistic effect; (+/-)-sulpiride and prazosin had a distinctly less potent action. Another effect of MK-801, anticonvulsant activity (electroshock-induced convulsions), was not increased by the antidepressants studied. These results indicate that antidepressants with a different pharmacological profile, increased the MK-801-induced locomotor hyperactivity, this effect being probably indirectly mediated, at least in part, by a dopamine mechanism.

Animals↗