Acute and chronic effects of desipramine administration to rhesus monkeys.

Rhesus monkeys were studied for changes in noradrenergic functioning before and after chronic oral administration (28 days) of the tricyclic antidepressant desipramine (DMI). Decreases in cerebrospinal fluid concentration of the norepinephrine metabolite MHPG were evident following the first dose (5.0 mg/kg) of DMI, but not after chronic administration of the drug. The alpha 2-adrenoceptor agonist clonidine reduced plasma norepinephrine prior to DMI treatment, but not after 28 days of treatment with DMI. These adaptive changes in noradrenergic function were evident in spite of very low plasma levels of DMI due to rapid metabolism of the drug in the rhesus monkey. The development of changes compatible with alpha 2-adrenoceptor subsensitivity in the presence of plasma levels of the drug that are well below those considered therapeutic in the treatment of depression suggests that such a receptor change may be dissociated from the drug's antidepressant effect.