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.