Subchronic treatment with the tricyclic antidepressant DMI increases isolation-induced fighting in rats.

Male rats treated with desmethylimipramine (DMI) (20 mg/kg for 7 days) were more likely than controls to attack an intruder rat placed in their home cage; they were also more likely to submit when attacked by the intruder. These behavioural changes were not seen at lower doses of DMI. Similar results were obtained in experiments in which is drugged animal and a control were placed together in a "neutral" cage; in this paradigm it was also found that lower doses of DMI were effective, provided that either the period of drug treatment was increased, or a delay of 3-4 days after withdrawal of DMI preceded behavioural testing. A dose dependent resistance to handling developed during drug treatment; drugged animals also showed weight loss and decreased open-field activity. In previous studies, acute treatment with tricyclic antidepressants has not been found to increase fighting; the present results underline the importance of chronic drug studies.