Noradrenaline in basic models of depression.
This review reports anatomical studies evaluating central and peripheral alpha 2- and beta-adrenoceptors. The results suggest abnormalities exist in the noradrenergic system in depressed patients. Most animal models involve the use of stress to simulate depression in man. All models that have been developed lead to differential changes in noradrenergic function. We have assessed the effects of reboxetine, a novel, selective noradrenaline-reuptake inhibitor (NARI) in olfactory bulbectomised rats, a procedure that induces significant changes in amygdala function. Reboxetine is an effective antidepressant in the forced swim test and open field test in bulbectomised rats. Unlike the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), reboxetine is ineffective in the 8-OH-DPAT hypothermia test, indicating that reboxetine is selective for the noradrenergic system. Owing to the abnormalities that occur in depression, it would seem sensible to target the noradrenergic system for treatment of this condition.
Leonard
B E
BE
Department of Pharmacology, University College, Galway, Ireland.
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D009025:Morpholines / Q000627:therapeutic use*; D009830:Olfactory Bulb; D000077593:Reboxetine; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D009025:Morpholines; D011941:Receptors, Adrenergic; D000077593:Reboxetine