The Density of N-Methyl-D-Aspartate Receptor in Rat Striatum Varies with Differing Psychotropic Drug Treatments

Abstract

Background: A number of studies in rodents suggest that antipsychotic drug treatment can either alter the levels or functionality of the N-methyl-D-aspartate receptor (NMDAR). This raises the possibility that some of the therapeutic actions or side-effects of antipsychotic drugs could be mediated through the NMDAR. Objective: To determine if treatments with combinations of psychotropic drugs change the levels of the NMDAR in rat Central Nervous System (CNS). Methods: In situ radioligand binding and autoradiography were used to quantify [3H]MK-801 binding to NMDAR in frozen CNS sections from rats treated with vehicle, haloperidol (0.1 mg/kg/day), olanzapine (1.0 mg/kg/ day), lithium (25.5 mg/kg/day) or, at the same doses, haloperidol and lithium or olanzapine and lithium for 28 days. Results: There was a significant variation of [3H]MK-801 binding with treatment in the rat striatum due to higher levels of radioligand in rats treated with haloperidol compared to those treated with olanzapine and lithium (p < 0.01; Cohen’s d = 1.47). Levels of radioligand binding did not vary with drug treatment in the cortex. Conclusion: These data argue for some effect of polypharmacy on NMDAR levels, possibly localized to the striatum. Further studies of mood stabilisers with known effects on NMDAR functionality, such as valproate and lamotrigine, with and without antipsychotic drugs could be worthwhile as they may show a greater effect on NMDAR density in the CNS. Keywords: Glutamate, haloperidol, lithium, olanzapine, NMDA, psychotropic drug.