Differential binding of [H-3]MK-801 to brain regions and spinal cord of mice treated chronically with morphine

1. The effects of morphine tolerance and abstinence on the binding of [H-3]MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors were determined in brain regions and spinal cord of the mouse. 2. Male Swiss-Webster mice were rendered tolerant to and physically dependent on morphine by subcutaneous implantation of a pellet containing 75 mg of morphine base for 3 days. Placebo pellet implanted mice served as controls. In tolerant (nonabstinent) mice, the pellets were left intact at the time of sacrificing whereas, in the abstinent mice, the pellets were removed 6 hr prior to sacrificing. 3. The binding of [H-3]MK-801 to membranes prepared from spinal cord and brain regions (cortex, pons medulla, hypothalamus, hippocampus, amygdala, striatum, and midbrain) was determined by using a 5 nM concentration of the ligand in the presence of 30 mu M glycine and 50 mu M of glutamate. 4. In nonabstinent morphine tolerant mice, the binding of [H-3]MK-801 was decreased in pons-medulla and hypothalamus, but was increased in the spinal cord in comparison to that in placebo controls. The reduction in binding in pons medulla was due to a decrease in the B-max value the K-d value remained unchanged. The binding of [H-3]MK-801 was increased in the hippocampus of morphine-abstinent mice. 5. These studies demonstrate that NMDA receptors of brain regions and spinal cord are differentially affected in morphine tolerant and abstinent mice.