Modification of the binding of [H]MK-801 to brain regions and spinal cord of rats treated chronically with U-50,488H, a κ-opioid receptor agonist

Male Sprague-Dawley rats were rendered tolerant to U-50,488H by twice-daily injections of the drug (25 mg/kg, i.p.) for 4 days. In tolerant rats, the binding of [³H]MK-801 was increased in pons and medulla and corpus striatum but decreased in midbrain and hippocampus and was due to changes in B_max values. In U-50,488H-abstinent rats, the binding of [³H]MK-801 was increased in pons and medulla and hippocampus, and decreased in midbrain and amygdala. In hippocampus, the B_max of [³H]MK-801 was increased but the K_d was decreased whereas in amygdala and pons and medulla, the changes were due to alterations in the B_max values. Previous studies have shown that NMDA receptor antagonists block the tolerance to the analgesic action of U-50,488H in rodents. The present studies demonstrate differential changes in the NMDA receptors of brain regions of U-50,488H-tolerant and -abstinent rats.