Behavioural evidence that chronic treatment with the antidepressant desipramine causes reduced functioning of brain noradrenaline systems.

A behavioral system sensitive to the net functional activity of the locus coeruleus noradrenergic system, with characteristics of a beta-adrenoceptor mediated response, has been developed based on the duration of thiopentone anaesthesia in the rat. The effects of acute and chronic treatment with the tricyclic antidepressant desipramine (DMI) were determined. Acute DMI from 5 to 25 mg/kg increased thiopentone sleeping-time in a dose-dependent fashion. This was due to an action on noradrenergic systems, since it was mimicked by treatment with the selective neurotoxin 6-hydroxydopamine, which itself increased thiopentone sleeping-time and prevented any additional effect of DMI. Chronic treatment with DMI had no effect on thiopentone sleeping-time when carried out for 2 or 5 days but markedly prolonged it when carried out for 10 or 20 days, thus paralleling the time course of clinical action of the drug.