Constant rate infusion of deuterated phosphorylcholine to measure the effects of morphine on acetylcholine turnover rate in specific nuclei of rat brain.
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Biomedical subjects
Publications and source records attributed to G Zsilla.
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Muscimol (8.8 mumol/kg i.v.) and diazepam (7.04 mumol/kg i.p.) decreased the rate of turnover of acetylcholine in midbrain and cortex of rat brain but failed to change acetylcholine turnover in striatum and hippocampus. The similarity in the profile of the action of diazepam and muscimol on acetylcholine turnover in various brain structures adds support to the view that GABA participates in mediating the actions of diazepam. Since the striatum contains an abundance of GABA neurones and intrinsic cholinergic neurones, it is inferred that the metabolism of acetylcholine, and presumably the activity of striatal cholinergic neurones are not regulated by the activation of GABA receptors. Similar considerations apply to the cholinergic pathway projecting from the septum to the hippocampus.
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In rats, an ED50 for analgesia of morphine, meperidine, viminol R2 or azidomorphine decreases the turnover rate of acetylcholine (TRACh) in cortex and hippocampus. These four analgetics fail to change to TRACh in striatum when given in a dose range from ED30 for analgesia up to a cataleptic dose. Viminol S2, a nonanalgesic stereoisomer of vimonol R2, fails to decrease the TRACh in cortex and hippocampus. Naltrexone, an opiate antagonist, also fails to change the cortical and hippocampal TRACh but it antagonizes the decrease in cortical and hippocampal TRACh elicited by the four analgetics. Since the ED50 of these four analgetics fails to change the TRACh in striatum which contains a high density of opiate receptors and intrinsic cholinergic neurons, but decreases the TRACh in hippocampus and cortex which contain a low density of opiate receptors, it can be inferred that opiate receptors are not exclusively involved in the regulation of TRACh. However, the results suggest that certain cholinergic pathways participate in the mediation of analgesia.
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The metabolism of [7,8-3H]azidomorphine and the in vivo stability of the azidogroup in azidomorphine and 14-hydroxyazidomorphine was studied. Asidomorphine conjugates with glucuronic acid, and is N-demethylated by rat liver microsomes. Detection by means of infrared spectroscopy proved that the azidroup in azidomorphine and 14-hydroxyazidomorphine strongly resists biotransformation in the rat.
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The action of clorgyline and (-)deprenyl on the dynamics of dopaminergic and serotonergic transmission in the rat brain was compared. It was found, that daily administration of 0.25 mg/kg sc clorgyline, a specific MAO A inhibitor, reduced the turnover rate of both dopamine and serotonin after two weeks of injections. The treatment for two or four weeks with 0.25 mg/kg sc (-)deprenyl, a specific MAO B inhibitor, enhanced the turnover rate of dopamine and the fractional rate constant of dopamine efflux, reflecting an increased utilization rate of this amine in the striatum. Beside the augmentation of the dopamine turnover rate, the dopaminergic tone was also elevated by the reduction of the dopamine uptake in the striatum. Two week injections with the same dose of (-)deprenyl did not change the dynamics of serotonergic transmission.