The effect of the NMDA receptor antagonist dizocilpine on behavioral manifestations of serotonin and adrenergic antidepressants in rats.
Glutamatergic neurotransmission has been implicated in affective disorders, possibly through the modulation of monoaminergic mechanisms. The aim of this study was to investigate the effect of coadministration of the noncompetitive NMDA antagonist dizocilpine (MK-801) with different, primarily noradrenergic and serotonergic antidepressants on forced swimming test (FST) and open-field behavior in rats. Acute administration of dizocilpine at doses of 0.02- 0.1 mg/kg did not show any effect in the open-field test or FST. Acute administration of citalopram (5 mg/kg), fluoxetine (20 mg/kg), desipramine (20 mg/kg) and maprotiline (20 mg/kg) did not influence FST, although coadministration of dizocilpine with serotonergic but not noradrenergic antidepressants caused a significant reduction of immobility. In the open-field test, fluoxetine had no effect on horizontal activity but significantly reduced the number of rearings. The coadministration of dizocilpine with fluoxetine elicited significant horizontal locomotor activation and attenuated the effect of fluoxetine on vertical activity. The combined administration of other antidepressants with dizocilpine tended to increase horizontal activity similar to that recorded with fluoxetine plus dizocilpine, but these effects were not statistically significant. Thus, the present results indicated that the coadministration of serotonergic antidepressants with NMDA receptor antagonists may induce faster and more pronounced antidepressant activity when compared to treatment with antidepressants alone. In contrast, the NMDA antagonists did not potentiate the antidepressant-like effects of noradrenergic antidepressants.
Pruus
K
K
Department of Pharmacology, University of Tartu, Tartu, Estonia. katrin.pruus@ut.ee
Rudissaar
R
R
Allikmets
L
L
Harro
J
J
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013550:Swimming
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D017367:Selective Serotonin Reuptake Inhibitors