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Action of various antidepressant treatments reduces reactivity of noradrenergic cyclic AMP-generating system in limbic forebrain

Naturevolume 257pages495496 (1975) | Download Citation



STUDIES on the pharmacology of the noradrenergic cyclic AMP-generating system in slices from the limbic forebrain of the rat1 and on adaptive properties of this system in conditions of persistent changes in the availability of nor-adrenaline (NA) have revealed that the system may serve as a model for the central NA receptor in this area, and that its sensitivity to NA increases or decreases when the availability of NA at the receptor site decreases or increases respectively2,3. Thus, hypersensitivity of the system has been achieved by treatment with reserpine2, a drug known to precipitate occasionally severe depressive reactions in man4, and the syndrome of which, when elicited in animals, is widely used as a model for depression5–7. Conversely, the monoamine oxidase (MAO) inhibitors, pargyline and nialamide, caused a marked reduction in the reactivity of the cyclic AMP-generating system to NA after chronic administration3. To determine whether or not antidepressant drugs which do not elevate the level of monoamines in brain share the effect of MAO inhibitors on the noradrenergic cyclic AMP-generating system, we studied the effect of the tricyclic antidepressants, desipramine and iprindole, on the reactivity of the system to NA. Desipramine blocks the uptake of NA through the neuronal membrane8,9 whereas iprindole neither blocks the neuronal uptake of NA nor alters its metabolism or turnover10,11, but is nevertheless a potent antidepressant12–14. In addition, we have tested the effect of electroconvulsive treatment (ECT), as it is generally accepted to be one of the most effective treatments for severe depression15.

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  1. Vanderbilt University School of Medicine and Tennessee Neuropsychiatric Institute, Nashville, Tennessee, 37232



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