Role of NMDA and AMPA glutamate receptors in the induction and the expression of dopamine-mediated sensitization in 6-hydroxydopamine-lesioned rats

Abstract

Rats with unilateral 6-hydroxydopamine (6-OHDA) lesions exhibit behavioral sensitization following repeated treatment with dopamine agonists, a phenomenon called "priming." Priming has two distinct phases: induction and expression. Priming induction using three injections with D1/D2 agonist apomorphine (0.5 mg/kg) or D1 agonist SKF38393 (10 mg/kg) allows priming expression, robust contralateral rotational behavior and striatal Fos expression, following a challenge with the D2 agonist quinpirole (0.25 mg/kg). We examined the roles of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors on dopamine agonist priming. Administration of the NMDA antagonist (+)5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK801) (0.5 mg/kg) blocked apomorphine-priming of quinpirole-mediated responses, while MK801 dose-dependently attenuated SKF38393-priming of quinpirole-mediated striatal Fos expression and had no effect on SKF38393-priming of quinpirole-mediated rotational behavior. In contrast, administration of the AMPA antagonist 2,3-dihydroxy-6-nitro-7sulfamoyl-benzo[f]quinoxaline (NBQX) (5 or 10 mg/kg) potentiated apomorphine- and SKF38393-priming of quinpirole-mediated striatal Fos expression, but had no effect on their priming of quinpirole-mediated rotational behavior. In SKF38393-primed 6-OHDA rats, administration of MK801 (0.5 mg/kg) blocked the expression of quinpirole-mediated responses, while administration of NBQX (10 mg/kg) or the noncompetitive AMPA antagonist 4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)-benzenamine dihydrochloride (GYKI52466) (5 or 15 mg/kg) had no effect. These results suggest that NMDA and AMPA glutamate receptors have differing roles in dopamine agonist priming-with NMDA receptors required for D1/D2 priming induction and D2-mediated priming expression, and AMPA receptors inhibiting priming induction of D2-mediated immediate early gene expression in the striatum, but not affecting priming induction of D2-mediated rotational behavior or the expression of D2-mediated responses.