Chronic carbamazepine decreases the incorporation rate and turnover of arachidonic acid but not docosahexaenoic acid in brain phospholipids of the unanesthetized rat: relevance to bipolar disorder.
BACKGROUND
The basis for carbamazepine's efficacy in treating bipolar disorder is not agreed on. One hypothesis is that, similar to lithium and valproate (antibipolar drugs), carbamazepine might selectively decrease the kinetics of arachidonic acid (AA) in brain phospholipids.


METHODS
To assess whether it targets brain AA kinetics, we administered carbamazepine (25 mg/kg/day, IP) to rats for 30 days and then determined its effect compared with that of vehicle on incorporation and turnover rates of AA and docosahexaenoic acid (DHA) in brain phospholipids. In unanesthetized rats that had received carbamazepine or vehicle, [1-14C]AA or [1-14C]DHA was infused intravenously, and arterial blood plasma was sampled until the animal was killed at 5 min and its brain, after being microwaved, was used for acyl-coenzyme A (acyl-CoA) and phospholipid fatty acid analysis.


RESULTS
Chronic carbamazepine, compared with vehicle, decreased the rate of incorporation of AA-CoA (27%-29%) and turnover of AA (25%-27%) but not of DHA-CoA or DHA in brain phospholipids.


CONCLUSIONS
The results, which are comparable to published findings after chronic administration of lithium and valproic acid to rats, support the hypothesis that drugs effective against mania in bipolar disorder act by selectively downregulating the incorporation rate of AA-CoA and turnover of AA in brain phospholipids.
Bazinet
Richard P
RP
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rao
Jagadeesh S
JS
Chang
Lisa
L
Rapoport
Stanley I
SI
Lee
Ho-Joo
HJ
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D001714:Bipolar Disorder / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology*; D003065:Coenzyme A / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D008134:Long-Term Care; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D016896:Treatment Outcome
D000214:Acyl Coenzyme A; D000927:Anticonvulsants; D018692:Antimanic Agents; D005227:Fatty Acids; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D002220:Carbamazepine; D003065:Coenzyme A