May 16, 2000

Antidepressant drug administration modifies the interactive relationship between alpha(2)-adrenergic sensitivity and levels of TNF in the rat brain

Journal of Neuroimmunology
T J NickolaR N Spengler

Abstract

A reciprocally permissive interaction occurs between cellular responses elicited by the pleiotropic cytokine tumor necrosis factor-alpha (TNF) and alpha(2)-adrenergic receptor activation, such that each may adapt in response to modifications in the other's effects. Changes in presynaptic adrenergic sensitivity as well as neuronal sensitivity to TNF have been implicated in the mechanism of action of antidepressant drugs. The present study examines the influence of alpha(2)-adrenergic receptor activation on levels of TNF in regions of the brain associated with adrenergic function and the expression of mood. Additionally, the role of TNF as a neuromodulator is demonstrated by in vivo microinfusion of rrTNF proximal to the hippocampus. Administration to rats of an alpha(2)-adrenergic receptor agonist (clonidine) decreases levels of TNF in homogenates of rat locus coeruleus and hippocampus within 7.5 min. Chronic (14 days) administration of the antidepressant drugs desipramine or zimelidine transforms alpha(2)-adrenergic receptor-dependent decreases in TNF levels to increases in levels of TNF in the locus coeruleus. This transformation to an increase in total levels of TNF also occurs, although transiently, in the hippocampus follow...Continue Reading

Mentioned in this Paper

ratio-Desipramine
Tumor Necrosis Factor-alpha
Neurotransmitter Secretion
Sympathetic Nervous System
Proteins, Recombinant DNA
Brain
Adrenergic Agonists
Entire Central Nervous System
Norepinephrine, (+, -)-Isomer
Structure of Locus Ceruleus

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