Effects of reboxetine and sertraline treatments alone and in combination on the binding properties of cortical NMDA and beta 1-adrenergic receptors in an animal model of depression

Changes to the binding properties of cortical N-methyl-D-aspartic acid (NMD A) and beta-adrenergic receptors have both been reported as potential indic ators of antidepressant activity. In the present investigation we examined the effects of the noradrenaline reuptake inhibitor, reboxetine, the seroto nin reuptake inhibitor, sertraline, alone and in combination on the binding properties of cortical NMDA receptors and cortical beta (1)-adrenoceptors following 14 days of treatment in the olfactory bulbectomized rat model of depression. A decrease in the potency of glycine to displace the strychnine insensitive glycine antagonist [H-3] 5,7 dichlorokynurenic acid (5,7 DCKA) was observed in cortical homogenates of OB rats when compared to sham-oper ated controls. Similarly, treatment with the combination of reboxetine and sertraline for 14 days produced a decrease in the potency of glycine when c ompared to vehicle treated controls. By contrast neither olfactory bulbecto my or drug treatment significantly altered basal or glycine enhanced bindin g of the non-competitive NMDA antagonist [H-3] MK-801 in cortical homogenat es. Reboxetine alone, and in combination with sertraline, down-regulated [H -3]-CGP 12177 (a selective beta -adrenoceptor antagonist) binding in both O B and sham-operated animals. The lack of a bulbectomy effect in the [H-3] C GP-12177 binding assay, and the fact that olfactory bulbectomy and antidepr essant treatments produce a similar change to the potency of glycine at the NMDA receptor, suggests that these tests do not provide a neurochemical ma rker for either the behavioral hyperactivity deficit or antidepressant resp onse in the model.