Changes in the sensitivity of the central alpha- and beta-adrenergic systems during desmethylimipramine treatment as assessed by plasma growth hormone response in the baboon.

Abstract

The tricyclic antidepressant desmethylimipramine (DMI) 2.5 mg/kg IM was administered to adolescent baboons once daily for 21 days, to investigate changes in alpha- and beta-noradrenergic function. Prior to DMI treatment, plasma growth hormone (GH) responses to the intravenous infusion of an alpha 2-adrenergic receptor agonist, clonidine, or a beta 2-adrenergic antagonist, ICI 118,551, were determined. DMI, 2.5 mg/kg, administered acutely did not stimulate the release of GH (up to 4 h post injection). The GH response to clonidine was decreased 4 h after DMI, 2.5 mg/kg. Alterations in plasma GH response to clonidine and ICI 118,551 were evident during and after chronic DMI administration. The GH response to clonidine was significantly diminished after 2 days, and gradually returned to the pretreatment amplitude over 7-21 days of treatment, with an overshoot 2 days after DMI withdrawal. After 21 days of DMI administration the GH response to ICI 118,551 was significantly enhanced, and remained consistently elevated during a withdrawal period of 21 days. These changes in the response to an alpha-adrenergic agonist and a beta-adrenergic antagonist indicate that the long term regulatory changes in receptor sensitivity, occurring between 2 and 21 days of DMI treatment, compensate for the acute effects of DMI on these responses.