Rats were chronically treated with methamphetamine over a seven week period during which time their weights, food consumption and drinking rates were recorded. The effects of chronic treatment with, and withdrawal from, methamphetamine on amine metabolism in selected brain regions was investigated. Three groups of experimental animals were studied: chronically treated rats, rats which had been withdrawn from the drug for 36 h and controls. The parameters chosen to reflect changes in catecholamine metabolism in the brain were: tyrosine hydroxylase activity and the levels of noradrenaline, dopamine and their non-O-methylated metabolites and of phenylalanine and tyrosine. The metabolism of serotonin was studied by measuring the levels of "free" tryptophan in the plasma,and the levels of tryptophan and serotonin in the brain. Initially the methamphetamine was administered in the drinking water at doses of 5, 10, 20 and 40 mg/kg/24 h increasing in a stepwise manner over a period of 20 days. This dose was found to produce toxic reactions in the rats and it was found that it was not possible to control the intake of the drug. In subsequent experiments the rats were given 5, 10 and 15 mg/kg/24 h i.p. increasing in a stepwise manner over a period of 15 days. The first set of injected animals did not develop tolerance to the anorexic effects of methamphetamine and the chronically treated and withdrawn animals showed changes in tyrosine hydroxylase activity and in the levels of noradrenaline and dopamine. The three other sets of injected animals did develop tolerance to the anorexic effects of methamphetamine. Tyrosine hydroxylase and the levels of noradrenaline, dopamine, their non-O-methylated metabolites and of tryptophan and serotonin did not change in these chronically-treated or withdrawn animals, but changes were seen in the levels of "free" tryptophan in the plasma and the levels of most amino acids in the brain.
|Date of Award||1978|