Dec 5, 1994

Tumor necrosis factor-alpha: presynaptic sensitivity is modified after antidepressant drug administration

Brain Research
T A Ignatowski, R N Spengler

Abstract

Presynaptic adrenergic functioning was coupled to cytokine sensitivity in order to further establish the mechanism of action of a tricyclic antidepressant drug. Antidepressant administration of desipramine to rats twice-daily for 2 weeks increased hippocampal TNF levels and transformed the presynaptic TNF response. One day of desipramine administration resulted in increased locus coeruleus TNF mRNA accumulation and, simultaneously, hippocampal TNF levels escalated. The fractional release of [3H]norepinephrine during field stimulation of control hippocampal slices was decreased by the addition of TNF in a concentration-dependent manner, an effect which was potentiated by the alpha 2-adrenergic antagonist idazoxan. While no change in sensitivity to TNF was observed in the hippocampus after one day of desipramine administration, TNF enhanced, rather than inhibited [3H]norepinephrine release after 14 days. In addition, TNF potentiation of [3H]norepinephrine release after chronic desipramine administration was reversed in the presence of idazoxan to a greater inhibition than in control slices exposed to idazoxan. Therefore, TNF-induced regulation of [3H]norepinephrine release appears to be associated with an alteration of alpha 2-ad...Continue Reading

  • References19
  • Citations23

Mentioned in this Paper

Necrosis
Presynaptic Terminals
ratio-Desipramine
Tumor Necrosis Factor-alpha
Sympathetic Nervous System
Neurons
Idazoxan
Norepinephrine, (+, -)-Isomer
Structure of Locus Ceruleus
Genus Hippocampus

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