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A large number of psychoactive drugs were tested on the aggressiveness induced by isolation; till now only ampizine, chlordiazepoxide and its derivatives have shown a certain degree of effectiveness. In aggressive animals the level of 5-hydroxyindolacetic acid was found to be consistently lower than in the controls while the turnover rates of serotonin and noradrenalin were found to increase. However, brain serotonin turnover could not be used to predict whether a strain of mice would or would not develop aggressiveness upon isolation. In addition in female mice, which consistently do not become aggressive after isolation, serotonin turnover rates were found to be higher than the turnover rates of the males of the same strain which do develop isolation aggressiveness. (Author)

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)