Differential binding of [3H]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 [3H]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 [3H]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 microM glycine and 50 microM of glutamate. 4. In nonabstinent morphine-tolerant mice, the binding of [3H]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 Bmax value; the Kd value remained unchanged. The binding of [3H]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.
Gudehithlu
K P
KP
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago 60612, USA.
Bhargava
H N
HN
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000506:poisoning*; D009021:Morphine Dependence / Q000378:metabolism; D009294:Narcotics / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D009294:Narcotics; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D009020:Morphine