Acute and chronic antidepressant drug treatments induce opposite effects in the social behaviour of rats

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Abstract
Clinical studies indicate that the behavioural responses/reactions of depressed patients to environmental and social stimulation are modified during remission from depressive illness, and require continuous (at least 3 weeks) drug treatment. In order to determine whether antidepressant drugs modify the behavioural patterns of experimental animals in ways that may be related to their ability to modify human reactive behaviour, we have examined the effects of acute and chronic treatment with clomipramine, fluoxetine, iprindole, mianserin and phenelzine (antidepressants with markedly different acute pharmacology) on the behaviour exhibited by rats during social interaction (SI). Acute treatment of short-term isolated resident rats with non-sedative doses of each antidepressant drug selectively and dose-relatedly reduced aggressive behaviour exhibited during SI. Conversely, haloperidol (antipsychotic) or diazepam (anxiolytic) only reduced aggressive behaviour at sedative doses. In comparison, following chronic treatment, all antidepressants examined, but not haloperidol or diazepam, increased aggressive behaviour exhibited by resident rats during SI which returned to the pre-treatment level by 7 or (after phenelzine) 14 days after the cessation of treatment. It is concluded that the antidepressants examined induce selective, diametrically opposite effects on rodent aggressive behaviour following acute and chronic treatment which is indicative of antidepressant efficacy. Furthermore, it is argued that the increased aggressive behaviour following chronic antidepressant drug treatment may indicate a disinhibition of social behaviour in the rat that mirrors the externalization of emotions associated with the remission of depressive illness.