Tricyclic antidepressant drug action correlates with its tissue levels in anterior neocortex

In the behavioral reversal of learned helplessness in the rat by imipramine, a strong correlation is found between "cure" of helplessness and drug level in anterior neocortex, the locus of drug action in this model of depression. This suggests that the delayed onset of therapeutic action of antidepressant drugs is due to the time required to achieve adequate drug levels at the site of their action.