Abstract
The effect of multiple intracerebroventricular (i.c.v.) injections of [D-Pen2, D-Pen5]enkephalin (DPDPE), a delta-opioid receptor agonist, on the activity of nitric oxide synthase (NOS) was determined in the brain regions and spinal cord of the mouse. Male Swiss Webster mice were injected twice daily with DPDPE (20 micrograms/mouse, i.c.v.) or its vehicle for 4 days. This procedure has previously been shown to induce tolerance to the antinociceptive actions of DPDPE in mice. On day 5, the animals treated with DPDPE were either sacrificed 20 min after an i.c.v. injection of DPDPE (tolerant) or without any injection (abstinent i.e., 16 h after the last injection of DPDPE). NOS activity in brain regions (cortex, striatum, hippocampus, midbrain, pons/medulla, hypothalamus and cerebellum) and spinal cord was determined by the rate of conversion of arginine into citrulline. Tolerance to DPDPE was associated increases in NOS activity in midbrain (49%) and pons/medulla (32%) and decreases in cerebellum (28%) and spinal cord (44%). However, NOS activity was unchanged in the cortex, corpus striatum, hippocampus and hypothalamus. On the other hand, during abstinence from DPDPE, NOS activity increased in midbrain (84%) and hypothalamus (35...Continue Reading
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