Changes in Norepinephrine Turnover in Rat Brain During Chronic Administration of Imipramine and Protriptyline: A Possible Explanation for the Delay in Onset of Clinical Antidepressant Effects
JOSEPH J. SCHILDKRAUT M.D.1,
ANDREW WINOKUR 2,
PAUL. R. DRASKÓCZY M.D.3, , and
JANET H. HENSLE 4
1 Director and Associate Professor of Psychiatry, Neuropsychopharmacology Laboratory, Massachusetts Mental Health Center, Harvard Medical School, Boston, Mass.
2 Medical student at Tufts University School of Medicine, Boston, Mass.
3 Pharmacologist and Lecturer on Pharmacology, Neuropsychopharmacology Laboratory, Massachusetts Mental Health Center, Harvard Medical School, Boston, Mass.
4 Member of the staff, Neuropsychopharmacology Laboratory, Massachusetts Mental Health Center, Harvard Medical School, Boston, Mass.
In this study the authors compare the effects of acute and chronic administration of the tricyclic antidepressants imipramine and protriptyline on the turnover and matabolism of norepinephrine in rat brain. The turnover of norepinephrine was decreased after acute administration but increased during chronic administration of these drugs. This increase in norepinephrine turnover occurred sooner when thyroxine was administered with the imipramine. This may help to explain why clinical antidepressant effects are generally observed only after chronic administration of imipramine or protriptyline and why thyroid hormone may accelerate and enhance the clinical antidepressant effects of imipramine.
