John Piletz1, Robert Baker, Angelos Halaris. 1. Department of Psychiatry and Behavioral Neuroscience, Loyola University Medical Center, Maywood, IL 60153, United States.
Abstract
OBJECTIVE: Previous studies have shown that imidazoline receptors (IR-1) are increased in platelets and frontal cortex of depressed patients, and this up-regulation is normalized (down-regulated) after antidepressant drug treatments. It has been hypothesized that IR-1 up-regulation during the depressive episode may be a state marker for depressive symptomatology. The goal of the present study was to address the state versus trait question. METHOD: Twelve healthy subjects (six males and six females) met stringent inclusion and exclusion criteria for physical and mental health. They received desipramine for 6 weeks in order to simulate the length of time and dosing used previously to obtain an IR-1 down-regulation and a therapeutic response in depressed patients. Outcome and safety measures included clinical, psychological, and cardiovascular assessments obtained throughout the study. Plasma concentrations of desipramine were measured throughout the 6 weeks of treatment and again after 2 weeks following tapered discontinuation of desipramine. Platelet receptors were assessed by Western blotting and radioligand binding assays. RESULTS: Healthy subjects taking desipramine experienced mild dysphoric effects but there were no adverse events. The binding of 8 nM p-[(125)I]clonidine to IR-1 and alpha(2)-adrenoceptors in healthy subjects did not change during desipramine treatment. The immunodensity of the 33 kDa band associated with IR-1 gradually increased to a maximum, by week-6, of 26% higher than baseline (p < 0.01 compared to baseline). Two weeks after desipramine discontinuation, there was a decline in alpha(2)-adrenoceptor binding and 33 kDa band's immunodensity (p = 0.04). CONCLUSIONS: The findings support the hypothesis that platelet IR-1 binding sites are a marker of mood state rather than of antidepressant-induced pharmacological regulation. By comparison, platelet alpha(2)-adrenoceptors appear to be regulated by desipramine as a pharmacological effect independent of mood state.
OBJECTIVE: Previous studies have shown that imidazoline receptors (IR-1) are increased in platelets and frontal cortex of depressedpatients, and this up-regulation is normalized (down-regulated) after antidepressant drug treatments. It has been hypothesized that IR-1 up-regulation during the depressive episode may be a state marker for depressive symptomatology. The goal of the present study was to address the state versus trait question. METHOD: Twelve healthy subjects (six males and six females) met stringent inclusion and exclusion criteria for physical and mental health. They received desipramine for 6 weeks in order to simulate the length of time and dosing used previously to obtain an IR-1 down-regulation and a therapeutic response in depressedpatients. Outcome and safety measures included clinical, psychological, and cardiovascular assessments obtained throughout the study. Plasma concentrations of desipramine were measured throughout the 6 weeks of treatment and again after 2 weeks following tapered discontinuation of desipramine. Platelet receptors were assessed by Western blotting and radioligand binding assays. RESULTS: Healthy subjects taking desipramine experienced mild dysphoric effects but there were no adverse events. The binding of 8 nM p-[(125)I]clonidine to IR-1 and alpha(2)-adrenoceptors in healthy subjects did not change during desipramine treatment. The immunodensity of the 33 kDa band associated with IR-1 gradually increased to a maximum, by week-6, of 26% higher than baseline (p < 0.01 compared to baseline). Two weeks after desipramine discontinuation, there was a decline in alpha(2)-adrenoceptor binding and 33 kDa band's immunodensity (p = 0.04). CONCLUSIONS: The findings support the hypothesis that platelet IR-1 binding sites are a marker of mood state rather than of antidepressant-induced pharmacological regulation. By comparison, platelet alpha(2)-adrenoceptors appear to be regulated by desipramine as a pharmacological effect independent of mood state.
Authors: D J Nutt; N French; S Handley; A Hudson; S Husbands; H Jackson; S Jordan; M D Lalies; J Lewis; L Lione Journal: Ann N Y Acad Sci Date: 1995-07-12 Impact factor: 5.691
Authors: P Ernsberger; M E Graves; L M Graff; N Zakieh; P Nguyen; L A Collins; K L Westbrooks; G G Johnson Journal: Ann N Y Acad Sci Date: 1995-07-12 Impact factor: 5.691
Authors: Benjamin Keller; Joan-Ignasi Mestre-Pinto; María Álvaro-Bartolomé; Diana Martinez-Sanvisens; Magí Farre; M Julia García-Fuster; Jesús A García-Sevilla; Marta Torrens Journal: Front Psychiatry Date: 2017-12-01 Impact factor: 4.157