Antidepressant drug administration modifies the interactive relationship between α2-adrenergic sensitivity and levels of TNF in the rat brain

Nickola, Tracey J.; Ignatowski, Tracey A.; Spengler, Robert N.

doi:10.1016/s0165-5728(00)00244-7

Cited by 18 publications

(28 citation statements)

References 26 publications

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“…5B (panel b), 6B (panel b), and 7). This finding supports previous results assessing bioactive TNFα production in these same regions following acute (either 1 day or 7.5-60 min) clonidine administration to rats (Ignatowski et al, 1996;Nickola et al, 2000). Of particular interest, the administration of clonidine to rats experiencing thermal hyperalgesia at day-8 post-ligature placement, when neuron-associated TNFα expression is increased (Figs.…”

Section: Effect Of α 2 -Adrenergic Receptor Activation On the Accumulsupporting

confidence: 90%

“…Immediately before decapitation, rats were returned to Plexiglas chambers, tested for thermal hyperalgesia, and decapitated at either 30 min or 120 min postinjection. The dose (0.2 mg/kg) of clonidine was selected for systemic administration based on our previously published reports on its affects on TNFα production in the brain (Ignatowski et al, 1996;Nickola et al, 2000) and that the appropriate analgesic dose of this drug is in the range of 0.006-2.0 mg/kg, with 0.2 mg/kg completely reversing carrageenan-induced thermal hyperalgesia (Sluka and Chandran, 2002).…”

Section: Drug Administration and Experimental Protocolmentioning

confidence: 99%

“…Based on these findings and to further study the role of TNFα in mediating hyperalgesia, the selective α 2 -adrenergic agonist, clonidine (0.2 mg/kg, i.p. ), a compound that affects levels of TNFα in the brain (Ignatowski et al, 1996;Nickola et al, 2000), was administered to rats experiencing peak hyperalgesia. Clonidine, also efficacious in alleviating chronic pain symptoms, when administered i.p.…”

Section: Treatment With Clonidine Attenuates Cci-induced Thermal Hypementioning

confidence: 99%

“…An interactive relationship occurs between inhibition of NE release by TNFα and α 2 -adrenergic agonists, and these responses transform such that both facilitate NE release during the resolution of neuropathic pain. In the present study, we tested the hypothesis that activation of the α 2 -adrenergic receptor, which directs TNFα production in the brain (Ignatowski et al, 1996;Nickola et al, 2000), reestablishes normal neuron functioning by treating rats undergoing neuropathic pain with the selective α 2 -adrenergic agonist, clonidine. Accumulation of mRNA for TNFα in noradrenergic brain regions (hippocampus and locus coeruleus) as well as TNFα and α 2 -adrenergic regulation of electrically-stimulated NE release from the hippocampus were assessed.…”

Section: Introductionmentioning

confidence: 99%

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Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

et al. 2007

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The central component that establishes chronic pain from peripheral nerve injury is associated with increased tumor necrosis factor-α (TNFα) production in the brain. This study examined TNFα and its reciprocally permissive role with α 2 -adrenergic activation during peak and progressive decline of thermal hyperalgesia in sciatic nerve chronic constriction injury (CCI). Accumulation of TNFα mRNA (in situ hybridization) increases in the hippocampus and locus coeruleus during the onset of neuropathic pain and persists as hyperalgesia abates. Activation of α 2 -adrenergic receptors in control rats decreases TNFα mRNA accumulation in these brain regions. In contrast, during hyperalgesia, α 2 -adrenergic activation enhances TNFα mRNA accumulation. Whether this enhanced TNFα production is associated with changes in the regulation of norepinephrine (NE) release was tested. Hippocampal slices were electrically depolarized to evaluate α 2 -adrenergic and TNFα regulation of NE release. While inhibition of NE release by TNFα is maximal during peak hyperalgesia, it subsequently transforms to facilitate NE release. In addition, α 2 -adrenergic receptor activation with clonidine (0.2 mg/kg, i.p.) in CCI rats experiencing hyperalgesia restores TNFα and α 2 -adrenergic inhibition of NE release. While TNFα directs the development of hyperalgesia, it also directs its resolution. Transformed sensitivity to α 2 -adrenergic agonists during hyperalgesia demonstrates a mechanism for therapy.

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Section: Effect Of α 2 -Adrenergic Receptor Activation On the Accumulsupporting

confidence: 90%

Section: Drug Administration and Experimental Protocolmentioning

confidence: 99%

Section: Treatment With Clonidine Attenuates Cci-induced Thermal Hypementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

et al. 2007

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“…Neuron exposure to TNF dictates their response to subsequent ␣ 2 -adrenergic receptor activation (Renauld et al, 2004) and vice versa (Nickola et al, 2000). Therefore, subsequent to sustained loss of neuron-associated TNF with chronic desipramine administration (Ignatowski et al, 1997;Nickola et al, 2001), the dynamic equilibrium between TNF production and ␣ 2 -adrenergic receptor activation is altered.…”

Section: Discussionmentioning

confidence: 99%

Brain-Derived Tumor Necrosis Factor-α and Its Involvement in Noradrenergic Neuron Functioning Involved in the Mechanism of Action of an Antidepressant

Reynolds

Ignatowski²,

Sud³

et al. 2004

J Pharmacol Exp Ther

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The present study documents a role for brain-derived tumor necrosis factor-␣ (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 ␣ 2 -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 release. These cellular events correspond to changes in immobility, analyzed by the forced swim test (FST). Intracerebroventricular microinfusion of rrTNF increases the duration of immobility of rats in the FST, compared with rats microinfused with aCSF. Desipramine administered chronically decreases immobility duration, which is mimicked by i.c.v. microinfusion of pTNF-Ab and prevented by simultaneous i.c.v. microinfusion of rrTNF. Thus, i.c.v. microinfusion of rrTNF with concomitant desipramine administration opposes decreases in neuron-associated TNF levels, required to transform presynaptic sensitivity to TNF, which is necessary for the drug to be efficacious.The etiology of depression as well as the mechanism of action of antidepressant drugs has been investigated for over 40 years, yet precise mechanisms that direct the expression of mood are unknown. Several theories have been postulated that implicate altered release of the neurotransmitter norepinephrine (NE) (Schildkraut, 1965) in the pathogenesis of depression. The classic Monoamine Theory of Depression proposes that symptoms of depression are due to an imbalance in the bioavailability of the monoamines, NE and serotonin, within the central nervous system (Schildkraut, 1965;Willner, 1985). Therefore, antidepressant drug-induced regulation of NE availability, as well as adrenergic receptors that regulate the release of NE, have been extensively investigated (Banerjee et al., 1977;Crews and Smith, 1978). A "dysregulation hypothesis" has also been proposed, which implicates an impaired negative feedback on presynaptic neurons due to dysfunctional presynaptic ␣ 2 -adrenergic receptors (Siever and Davis, 1985;Maes et al., 1999). These receptors are primary regulators of NE release from noradrenergic neurons and are classically known to ...

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Tumor necrosis factor expressed by primary hippocampal neurons and SH‐SY5Y cells is regulated by α₂‐adrenergic receptor activation

Renauld

Spengler

2001

J of Neuroscience Research

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Neuron expression of the cytokine tumor necrosis factor-alpha (TNF), and the regulation of the levels of TNF by alpha(2)-adrenergic receptor activation were investigated. Adult rat hippocampal neurons and phorbol ester (PMA)-differentiated SH-SY5Y cells were examined. Intracellular levels of TNF mRNA accumulation, as well as TNF protein and that released into the supernatant were quantified by in situ hybridization, immunocytochemistry and bioanalysis, respectively. Both neuron cultures demonstrated constitutive production of TNF. Activation of the alpha(2)-adrenergic receptor increased intracellular levels of TNF mRNA and protein in SH-SY5Y cells after addition of graded concentrations of the selective agonist, Brimonidine (UK-14304) to parallel cultures. Intracellular levels of mRNA were increased in a concentration-dependent fashion within 15 min of UK-14304 addition and were sustained during 24 hr of receptor activation. In addition, the levels of TNF in the supernatant were increased in both types of neuron cultures within 15 min of alpha(2)-adrenergic receptor activation. Furthermore, levels of TNF significantly increased in the supernatants of both neuron cultures after potassium-induced depolarization. A reduction in this depolarization-induced release occurred in hippocampal neuron cultures after exposure to the sympathomimetic tyramine with media replacement to deplete endogenous catecholamines. This finding reveals a role for endogenous catecholamines in the regulation of TNF production. Potassium-induced depolarization resulted in the release of TNF in hippocampal neuron cultures within 15 min but not until 24 hr in SH-SY5Y cultures demonstrating a temporally mediated event dependent upon cell type. Neuron expression of TNF, regulated by alpha(2)-adrenergic receptor activation demonstrates not only how a neuron controls its own production of this pleiotropic cytokine, but also displays a normal role for neurons in directing the many functions of TNF.

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Antidepressant drug administration modifies the interactive relationship between α2-adrenergic sensitivity and levels of TNF in the rat brain

Cited by 18 publications

References 26 publications

Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

Brain-Derived Tumor Necrosis Factor-α and Its Involvement in Noradrenergic Neuron Functioning Involved in the Mechanism of Action of an Antidepressant

Tumor necrosis factor expressed by primary hippocampal neurons and SH‐SY5Y cells is regulated by α₂‐adrenergic receptor activation

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Antidepressant drug administration modifies the interactive relationship between α2-adrenergic sensitivity and levels of TNF in the rat brain

Cited by 18 publications

References 26 publications

Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

Brain-Derived Tumor Necrosis Factor-α and Its Involvement in Noradrenergic Neuron Functioning Involved in the Mechanism of Action of an Antidepressant

Tumor necrosis factor expressed by primary hippocampal neurons and SH‐SY5Y cells is regulated by α2‐adrenergic receptor activation

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Tumor necrosis factor expressed by primary hippocampal neurons and SH‐SY5Y cells is regulated by α₂‐adrenergic receptor activation