Apr 15, 2004

Brain-derived tumor necrosis factor-alpha and its involvement in noradrenergic neuron functioning involved in the mechanism of action of an antidepressant

The Journal of Pharmacology and Experimental Therapeutics
J L ReynoldsR N Spengler


The present study documents a role for brain-derived tumor necrosis factor-alpha (TNF) in the mechanism of action of the antidepressant drug desmethylimipramine (desipramine). To establish this role, field stimulation and superfusion of rat hippocampal slices was employed to investigate the regulation of norepinephrine (NE) release by TNF. Chronic desipramine administration transforms TNF-mediated inhibition of NE release to facilitation, dependent upon alpha2-adrenergic receptor activation. Chronic i.c.v. microinfusion of polyclonal TNF antibody (pTNF-Ab) similarly transforms TNF inhibition of NE release to facilitation. To determine whether this transformation is due to desipramine-induced inhibition of TNF bioactivity in the brain, rats were i.c.v. microinfused with recombinant rat TNF (rrTNF) for 14 days, either alone or with simultaneous i.p. desipramine administration. TNF regulation of NE release in hippocampal slices isolated from these rats was compared with slices isolated from rats chronically administered desipramine alone. Although simultaneous microinfusion of rrTNF with chronic desipramine administration prevents the transformation induced by desipramine, microinfusion of rrTNF enhances TNF inhibition of NE relea...Continue Reading

Mentioned in this Paper

Presynaptic Terminals
Tumor Necrosis Factor-alpha
Norepinephrine, (+, -)-Isomer
Noradrenergic Neurons
Norepinephrine Measurement
Desipramine Measurement

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