Chronic fluoxetine upregulates arachidonic acid incorporation into the brain of unanesthetized rats.

Serotonergic 5-HT(2A/2C) receptors can be coupled to phospholipase A(2) (PLA(2)) activation to release the second messenger, arachidonic acid (AA), from membrane phospholipids. We wished to see if this signaling process in rat brain would be altered by chronic administration followed by 3days of washout of the selective serotonin reuptake inhibitor, fluoxetine. We injected [(3)H]AA intravenously in unanesthetized rats and used quantitative autoradiography to determine the incorporation coefficient k() for AA (regional brain radioactivity/integrated plasma radioactivity), a marker of PLA(2) activation, in each of 86 brain regions.

D2 but not D1 dopamine receptor stimulation augments brain signaling involving arachidonic acid in unanesthetized rats.

Rationale And Objectives: Signal transduction involving the activation of phospholipase A2 (PLA2) to release arachidonic acid (AA) from membrane phospholipids, when coupled to dopamine D1- and D2-type receptors, can be imaged in rats having a chronic unilateral lesion of the substantia nigra. It is not known, however, if the signaling responses occur in the absence of a lesion. To determine this, we used our in vivo fatty acid method to measure signaling in response to D1 and D2 receptor agonists given acutely to unanesthetized rats.

Chronic lithium administration to rats selectively modifies 5-HT2A/2C receptor-mediated brain signaling via arachidonic acid.

The effects of chronic lithium administration on regional brain incorporation coefficients k* of arachidonic acid (AA), a marker of phospholipase A2 (PLA2) activation, were determined in unanesthetized rats administered i.p. saline or 1 mg/kg i.

Chronic lithium administration potentiates brain arachidonic acid signaling at rest and during cholinergic activation in awake rats.

Studies were performed to determine if the reported 'proconvulsant' action of lithium in rats given cholinergic drugs is related to receptor-initiated phospholipase A2 signaling via arachidonic acid. Regional brain incorporation coefficients k* of intravenously injected [1-14C]arachidonic acid, which represent this signaling, were measured by quantitative autoradiography in unanesthetized rats at baseline and following administration of subconvulsant doses of the cholinergic muscarinic agonist, arecoline. In rats fed LiCl for 6 weeks to produce a therapeutically relevant brain lithium concentration, the mean baseline values of k* in brain auditory and visual areas were significantly greater than in rats fed control diet.

Imaging brain phospholipase A2-mediated signal transduction in response to acute fluoxetine administration in unanesthetized rats.

Fluoxetine, a selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor, is used widely to treat depression and related disorders. By inhibiting presynaptic 5-HT reuptake, fluoxetine is thought to act by increasing 5-HT in the synaptic cleft, thus 5-HT binding to postsynaptic 5-HT(2A/2C) receptors. These receptors can be coupled via a G-protein to phospholipase A(2) (PLA(2)), which when activated releases the second messenger arachidonic acid from synaptic membrane phospholipids.

Lithium chloride, administered chronically to rats, does not affect the fractional phosphorylation of brain cytosolic phospholipase A2, while reducing its net protein level.

Lithium, used to treat bipolar disorder, has been reported to decrease rat brain mRNA and protein levels of cytosolic phospholipase A(2) (cPLA(2)), an enzyme that selectively hydrolyzes arachidonic acid from the stereospecifically numbered (sn)-2 position of membrane phospholipids, and to decrease PLA(2) activity. cPLA(2) can be activated by being phosphorylated at its Ser-228, Ser-505, and Ser-727 sites. In this study, we show that the percent phosphorylated cPLA(2) protein in rat brain is unaffected by lithium.

Chronic lithium chloride administration to rats decreases brain protein level of epsilon (epsilon) subunit of eukaryotic initiation factor-2B.

The eukaryotic initiation factor-2B (eIF-2B) can regulate translation and protein synthesis. We used Western blot analysis to quantify the protein level of the catalytic epsilon (epsilon) subunit of eIF-2B in brains of rats fed lithium chloride (LiCl) for 6 weeks so as to produce a brain lithium concentration that is therapeutically effective in bipolar disorder. The ratio of eIF-2B (epsilon) to actin protein was significantly reduced (P<0.

Analysis of gene expression with cDNA microarrays in rat brain after 7 and 42 days of oral lithium administration.

The gene expression profile in rat brain was examined using microarrays in rats fed lithium chloride for 7 days (subacute) or 42 days (chronic). Brain lithium concentrations were 0.39 mM and 0.