Lithium decreases turnover of arachidonate in several brain phospholipids

Chang, Michael; Grange, Eric; Rabin, Olivier; Bell, Jane M.; Allen, David; Rapoport, Stanley I.

doi:10.1016/s0304-3940(96)13264-x

Cited by 147 publications

(169 citation statements)

References 16 publications

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“…Its cPLA 2 effect may be due a lithium-induced downregulation of Ca 2 + -dependent PKC, to reduce expression of PKC-dependent AP-2, which regulates cPLA 2 transcription (Rao et al, 2005;Wang et al, 2001). Consistent with selective cPLA 2 targeting, the LiCl diet reduces incorporation and turnover rates of AA but not of DHA in brain phospholipids of unanesthetized rats (Chang et al, 1996). Thus, one explanation for its suppression of the NMDA-induced increments in k* for AA in the present study is that it directly reduces the cPLA 2 activation response to increased intracellular Ca 2 + .…”

Section: Discussionmentioning

confidence: 86%

“…This study shows that (1) the in vivo fatty acid method (see Introduction) (Rapoport, 2001(Rapoport, , 2003 can be used to image PLA 2 activation coupled to NMDARs in unanesthetized rats; (2) regional increments in k* for AA in response to subconvulsant NMDA doses in control diet rats are blocked by pretreatment with MK-801; (3) MK-801 alone (or when given prior to 50 mg/kg NMDA) produces widespread baseline reductions in k* for AA in control diet rats; and (4) a 6-week LiCl diet, sufficient to produce plasma and brain lithium concentrations therapeutically relevant to BD (Bosetti et al, 2002b;Chang et al, 1996), largely (97%) prevents the significant NMDA-induced increments in k* seen in control diet rats.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, we measured k* for AA in response to NMDA in animals fed a control or LiCl diet for 6 weeks. The LiCl diet produces plasma and brain lithium concentrations of about 0.8 mM, reported to be therapeutic in BD (Basselin et al, 2003;Bosetti et al, 2002b;Calabrese et al, 1995;Chang et al, 1996). An abstract of part of this work has been presented (Basselin et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Basselin

Chang

Bell

et al. 2005

Neuropsychopharmacol

106

132

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It has been proposed that lithium is effective in bipolar disorder (BD) by inhibiting glutamatergic neurotransmission, particularly via N-methyl-D-aspartate receptors (NMDARs). To test this hypothesis and to see if the neurotransmission could involve the NMDARmediated activation of phospholipase A 2 (PLA 2 ), to release arachidonic acid (AA) from membrane phospholipid, we administered subconvulsant doses of NMDA to unanesthetized rats fed a chronic control or LiCl diet. We used quantitative autoradiography following the intravenous injection of radiolabeled AA to measure regional brain incorporation coefficients k* for AA, which reflect receptormediated activation of PLA 2 . In control diet rats, NMDA (25 and 50 mg/kg i.p.) compared with i.p. saline increased k* significantly in 49 and 67 regions, respectively, of the 83 brain regions examined. The regions affected were those with reported NMDARs, including the neocortex, hippocampus, caudate-putamen, thalamus, substantia nigra, and nucleus accumbens. The increases could be blocked by pretreatment with the specific noncompetitive NMDA antagonist MK-801 ((5R,10S)-( + )-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine hydrogen maleate) (0.3 mg/kg i.p.), as well by a 6-week LiCl diet sufficient to produce plasma and brain lithium concentrations known to be effective in BD. MK-801 alone reduced baseline values for k* in many brain regions. The results show that it is possible to image NMDA signaling via PLA 2 activation and AA release in vivo, and that chronic lithium blocks this signaling, consistent with its suggested mechanism of action in BD.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Basselin

Chang

Bell

et al. 2005

Neuropsychopharmacol

106

132

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“…For example, chronic LiCl like chronic CBZ blocked quinpirole-induced increments in k* for AA (we have not as yet examined lithium's ability to block the PGE 2 increment following quinpirole). Both chronic LiCl and CBZ reduced AA turnover in rat brain phospholipids, brain mRNA, protein and activity levels of cPLA 2 , and the DNAbinding capacity and protein level of a cPLA 2 transcription factor, activator protein-2 [11,19,27,42,43,45]. These observations, plus clinical data that dopaminergic neurotransmission is disturbed in bipolar disorder [13,28,31], and that dopamine receptor antagonists can be therapeutic whereas drugs that stimulate dopamine synthesis, bind to dopamine receptors or reduce dopamine reuptake often precipitate mania (see "Introduction"), suggest that mood stabilizers are therapeutic in bipolar disorder in part by suppressing excessive D 2 -like receptor signaling involving AA.…”

Section: Discussionmentioning

confidence: 98%

Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

et al. 2008

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Observations that dopaminergic antagonists are beneficial in bipolar disorder and that dopaminergic agonists can produce mania suggest that bipolar disorder involves excessive dopaminergic transmission. Thus, mood stabilizers used to treat the disease might act in part by downregulating dopaminergic transmission. In agreement, we reported that dopamine D 2 -like receptor mediated signaling involving arachidonic acid (AA, 20:4n-6) was downregulated in rats chronically treated with lithium. To see whether chronic carbamazepine, another mood stabilizer, did this as well, we injected i.p. saline or the D 2 -like receptor agonist, quinpirole (1 mg/kg), into unanesthetized rats that had been pretreated for 30 days with i.p. carbamazepine (25 mg/kg/day) or vehicle, and used quantitative autoradiography to measure regional brain incorporation coefficients (k*) for AA, markers of signaling. We also measured brain prostaglandin E 2 (PGE 2 ), an AA metabolite. In vehicle-treated rats, quinpirole compared with saline significantly increased k* for AA in 35 of 82 brain regions examined, as well as brain PGE 2 concentration. Affected regions belong to dopaminergic circuits and have high D 2 -like receptor densities. Chronic carbamazepine pretreatment prevented the quinpirole-induced increments in k* and in PGE 2 . These findings are consistent with the hypothesis that effective mood stabilizers generally downregulate brain AA signaling via D 2 -like receptors, and that this signaling is upregulated in bipolar disorder.

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“…One group of rats was fed ad libitum Purina Rat Chow (Harlan Telkad, Madison, WI) containing 1.70 g LiCl/kg for 4 weeks, followed by a diet containing 2.55 g LiCl/kg for 2 weeks (Basselin et al, 2003b). This feeding regimen produces 'therapeutically equivalent' plasma and brain lithium levels of about 0.7 mM (Bosetti et al, 2002;Chang et al, 1996). Control rats were fed lithium-free Purina rat chow under parallel conditions.…”

Section: Animals and Dietsmentioning

confidence: 99%

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Basselin

Chang

Seemann

et al. 2004

Neuropsychopharmacol

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The effects of chronic lithium administration on regional brain incorporation coefficients k* of arachidonic acid (AA), a marker of phospholipase A 2 (PLA 2 ) activation, were determined in unanesthetized rats administered i.p. saline or 1 mg/kg i.p. (7)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), a 5-HT 2A/2C receptor agonist. After injecting [1-14 C]AA intravenously, k* (brain radioactivity/integrated plasma radioactivity) was measured in each of 94 brain regions by quantitative autoradiography. Studies were performed in rats fed a LiCl or a control diet for 6 weeks. In the control diet rats, DOI significantly increased k* in widespread brain areas containing 5-HT 2A/2C receptors. In the LiCl-fed rats, the significant positive k* response to DOI did not differ from that in control diet rats in most brain regions, except in auditory and visual areas, where the response was absent. LiCl did not change the head turning response to DOI seen in control rats. In summary, LiCl feeding blocked PLA 2 -mediated signal involving AA in response to DOI in visual and auditory regions, but not generally elsewhere. These selective effects may be related to lithium's therapeutic efficacy in patients with bipolar disorder, particularly its ability to ameliorate hallucinations in that disease.

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Lithium decreases turnover of arachidonate in several brain phospholipids

Cited by 147 publications

References 16 publications

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

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