Afrri Sr74-9 May 1974 Afrri Scientific Report Morphine-induced Changes in the Activity of Enzymes Involved in Neurotransmitter Metabolism in Specific Brain Regions of the Tolerant Rat

The morphine-induced changes in the activity of enzymes involved in the metabolism of neurotransmitters in specific areas of the brain of rats made tolerant to morphine have been investigated. The activities of choline acetyl transferase (E.G.2.3.1.6.), acetylcholinesterase (E.C.3.1.1.7.) and monoamine oxidase (E.G. 1.4.3.4.) were determined in the hippocampus, thalamus, hypothalamus, cerebral cortex and basal ganglia of groups of rats sacrificed at predetermined times following the last scheduled morphine injection. It was found that, in animals that showed a paradoxical activation reaction shortly after the last morphine injection ("jumping" rats), monoamine oxidase activity decreased in all brain areas studied with lowest values between approximately 30 and 60 minutes, and returned to nearly normal values by 6 hours postinjection. Acetylcholinesterase activity showed oscillations above control values. Oscillating changes were also observed in the activity of choline acetyl transferase depending on the time of sacrifice of the animal. No appreciable changes in monoamine oxidase activity were observed in "nonjumping" tolerant rats.