The effects of acute and chronic administration of tricyclic antidepressants on MHPG-SO₄ in rat brain

The effects of acute and chronic administration of various tricyclic antidepressants on the levels of 3-methoxy-4-hydroxyphenylglycol sulfate (MHPG-SO₄), the principal metabolite of NE in rat brain were examined. The levels of MHPG-SO₄ were significantly decreased after acute administration of desmethyl-imipramine or imipramine and tended to be decreased after nortriptyline but not after amitriptyline. However, after chronic administration for two weeks, the levels of MHPG-SO₄ were significantly increased by desmethylimipramine or imipramine and were slightly increased by nortriptyline or amitriptyline. These results may help to explain why sustained treatment with tricyclic antidepressants is required to achieve clinical antidepressant effects.