Effect of 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline on Methamphetamine- and Cocaine-Induced Behavioral Sensitization

Abstract

The present study investigated the effect of pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, on behavioral sensitization induced by methamphetamine (METH) and cocaine at doses that are transitional relative to the induction of an acute response of locomotion and interrupting episodes of sniffing and head movement. Male Sprague–Dawley rats were randomly assigned to four groups that received daily either 20 mg/kg NBQX + 3 mg/kg METH, 40 mg/kg NBQX + 3 mg/kg METH, vehicle + 3 mg/kg METH, or vehicle + saline daily for 10 days. In another experiment, rats of four groups received daily either 20 mg/kg NBQX + 15 mg/kg cocaine, 40 mg/kg NBQX + 15 mg/kg cocaine, vehicle +15 mg/kg cocaine, or vehicle + saline daily for 10 days. NBQX did not attenuate activity/stereotypy induced by acute administration of either psychostimulant. Pretreatment with NBQX did not affect augmentation of activity/stereotypy scores by repeated administration of METH or cocaine. There was no significant difference in the intensity of activity/stereotypy between the NBQX + METH and vehicle + METH groups and between the NBQX + cocaine and vehicle + cocaine groups following a challenge injection with 2 mg/kg METH alone or 15 mg/kg cocaine alone, respectively, given 7 days after the last dose of repeated treatment session. Pretreatment with NBQX alone for 10 days (20 mg/kg for 5 days and 40 mg/kg for subsequent 5 days) did not affect the intensity of activity/stereotypy induced by a challenge injection with 2 mg/kg METH given 7 days after the last dose of repeated injection session. NBQX at 40 mg/kg had no apparent effect on acute METH (3 mg/kg)-induced dopamine release in the striatum. These results suggest tht AMPA receptors are unlikely to be involved in induction of behavioral sensitization that is manifested as augmented activity/stereotypy following repeated administration of METH or cocaine.