RETRACTED ARTICLE: Chronic fluoxetine increases cytosolic phospholipase A2 activity and arachidonic acid turnover in brain phospholipids of the unanesthetized rat

Abstract

The results support the hypothesis that fluoxetine increases the cPLA(2)-mediated turnover of AA within brain phospholipids.

Chronic lamotrigine does not alter the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat: implications for the treatment of bipolar disorder

“…The baseline concentrations of plasma unesterified fatty acids, brain esterified fatty acids, brain acyl-CoA species, and arachidonic acid kinetics in controls are similar to previous reports Lee et al 2005Lee et al , 2007. In conclusion, chronic administration of lamotrigine does not alter the turnover of arachidonic acid in brain phospholipids of the unanesthetized rat.…”

“…As in our previous reports Lee et al 2005Lee et al , 2007, HPLC separation of fatty acid methylester derivatives from pooled plasma total lipid extracts confirmed that 98% of total plasma lipid radioactivity represented labeled arachidonic acid after 5 min of infusion of [1− 14 C]arachidonic acid in both the lamotrigine-treated and the control rats. HPLC separation of fatty acid methyl ester derivatives from pooled brain total lipids extracts also showed that 96% of total brain radioactivity was in the form of [1− 14 C]arachidonic acid in both the lamotriginetreated and the control rats.…”

“…Dopamine D 2 receptors are coupled to cPLA 2 via a G protein-mediated mechanism (Piomelli et al 1991), which upon activation, releases arachidonic acid from brain phospholipids of the unanesthetized rat (Bhattacharjee et al 2005(Bhattacharjee et al , 2006. 5-HT 2A/2C receptors can be coupled to PLA 2 (Felder et al 1990), which upon activation, also releases unesterified arachidonic acid from rat brain phospholipids (Basselin et al 2005b;Lee et al 2007). The lack of effect of chronic lamotrigine on brain arachidonic acid turnover in the current study is consistent with the report that 5-HT and dopamine levels return to control values by 21 days (Ahmad et al 2004).…”

Chronic Administration of Lamotrigine Downregulates COX-2 mRNA and Protein in Rat Frontal Cortex

“…In contrast, classical antidepressants do not appear to add to efficacy of treatment [36], and frequently switch the depressive state to mania when administered alone to bipolar patients. While the switching tendency is not understood, studies in rats chronically administered the antidepressant fluoxetine, a selective serotonin reuptake inhibitor, indicate that this antidepressant upregulates markers of the brain arachidonic acid cascade: arachidonic acid turnover in brain phospholipids and brain activity, protein and mRNA levels of cPLA 2 [33,37]. Thus, the ability of lamotrigine to downregulate COX-2 rather than upregulate arachidonic acid cascade markers as does fluoxetine, may explain why lamotrigine does not promote switching when given to depressed bipolar patients, whereas fluoxetine does.…”

Is the brain arachidonic acid cascade a common target of drugs used to manage bipolar disorder?

“…In contrast with lithium, valproic acid and carbamazepine, chronic fluoxetine increased the turnover of arachidonic acid in rat brain phospholipids (Figure 2). The increase in arachidonic acid turnover was also associated with increased cPLA 2 activity, protein and mRNA expression [79,80]. Unlike chronic lithium and carbamazepine, fluoxetine did not target AP-2-binding activity, but did increase protein levels of nuclear AUF-1 [AU-rich element/poly(U)-binding/degradation factor-1], possibly increasing the half-life of cPLA 2 mRNA.…”