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

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Abstract

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 D2-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 D2-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 E2 (PGE2), 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 PGE2 concentration. Affected regions belong to dopaminergic circuits and have high D2-like receptor densities. Chronic carbamazepine pretreatment prevented the quinpirole-induced increments in k* and in PGE2. These findings are consistent with the hypothesis that effective mood stabilizers generally downregulate brain AA signaling via D2-like receptors, and that this signaling is upregulated in bipolar disorder.

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Abbreviations

AA:

Arachidonic acid

PLA2 :

Phospholipase A2

cPLA2 :

Cytosolic PLA2

sn :

Stereospecifically numbered

NMDA:

N-methyl-D-aspartate

CBZ:

Carbamazepine

PGE2 :

Prostaglandin E2

TXB2 :

Thromboxane B2

COX:

Cyclooxygenase

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Acknowledgments

This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. None of the authors has a financial or other conflict of interest related to this work.

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Authors and Affiliations

  1. Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bldg. 9, Room 1S126, Bethesda, MD, 20892, USA

    Mireille Basselin, Lisa Chang, Mei Chen, Jane M. Bell & Stanley I. Rapoport

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  1. Mireille Basselin
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  2. Lisa Chang
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  3. Mei Chen
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  4. Jane M. Bell
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  5. Stanley I. Rapoport
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Correspondence to Mireille Basselin.

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Basselin, M., Chang, L., Chen, M. et al. Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain. Neurochem Res 33, 1373–1383 (2008). https://doi.org/10.1007/s11064-008-9595-y

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