PHARMACOLOGICAL AND BIOCHEMICAL CHANGES IN ANIMALS MADE AGGRESSIVE BY ISOLATION.
Final technical rept. May 68-Apr 69,
ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI MILAN (ITALY)
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The aggressiveness induced by prolonged isolation in certain strains of mice represents a good behavioral model to study the activity of the psychoactive drugs as well as the changes of the brain biochemistry. Among the drugs tested for their activity on aggressive mice, few of them showed an antiagressive activity chlordiazepoxide seems to be, till now, the most interesting compound under this aspect, particularly when its action is considered in relation to the effect demonstrated upon the modification of brain N-acetyl-L-aspartic acid present in aggressive animals. From the biochemical point of view, the decrease of brain 5-hydroxytryptamine turnover in aggressive mice seems to be dependent neither on a different utilization of injected tryptophan, in comparison with normal animals, nor on a clear different monoamineoxidase activity. Moreover, no differences exist in acetylcholine formation in brain of aggressive and normal mice. Concerning the evaluation of the higher nervous functions the exploratory behavior appears to be drastically impaired in aggressive mice and chlordiazepoxide, among the various drugs tested, shows a strong efficacy in correcting the performance of these animals. Finally, prolonged isolation is able to induce aggressive reaction, of muricide type, in rats and also in these animals it is possible to detect a decrease of brain 5-hydroxytryptamine turnover. The experimental evidences indicate that aggressiveness by prolonged isolation is a good tool to study the neurochemical correlates of behavior as well as the activity and perhaps the mechanisms of action of the psychotropic drugs. Author