Behavioural changes during withdrawal from desmethylimipramine (DMI). II. Increased resistance to extinction.

Rats withdrawn from chronic treatment with the tricyclic antidepressant desmethylimipramine (DMI) showed increased resistance to extinction in a runway and in continuously reinforced lever pressing. Changes were not seen in animals maintained on DMI. In acquisition, in the runway, there were no significant differences between groups; in the Skinner box, animals maintained on DMI performed worse than controls, but withdrawn animals recovered to control levels of performance. It is suggested that the effect on extinction may be mediated by a decrease in the efficacy of the dorsal noradrenaline bundle, which develops during chronic DMI treatment, but is masked by the presence of DMI. The implications of the conclusion for the " revised catecholamine hypothesis of depression" are discussed.