Chronic lamotrigine does not alter the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat: implications for the treatment of bipolar disorder.
BACKGROUND
Drugs that are effective in treating the manic phase of bipolar disorder (lithium, carbamazepine, and valproate) upon chronic administration to rats decrease the turnover of arachidonic acid in their brain phospholipids. Lamotrigine may not be effective in the manic phase, but is effective in delaying the depressive phase and for treating rapid cycling bipolar disorder. Thus, lamotrigine provides a pharmacological tool to differentiate if downregulation of arachidonic acid turnover is specific to drugs effective in the manic phase of bipolar disorder.


METHODS
To test this hypothesis, rats were administered lamotrigine (10 mg kg(-1) day(-1)) or vehicle intragastrically once daily for 42 days. In the unanesthetized rat, [1-(14)C]arachidonic acid was infused intravenously and arterial blood plasma was sampled until the animal was killed at 5 min, and its microwaved brain was subjected to chemical and radiotracer analysis.


RESULTS
Using equations from our fatty acid model, we found that chronic lamotrigine compared with vehicle did not alter the net incorporation rate of plasma arachidonic acid into brain phospholipids, nor did it alter the turnover of arachidonic acid within brain phospholipids.


CONCLUSIONS
Chronic lamotrigine, which is effective in the depressive phase or rapid cycling bipolar disorder does not alter brain arachidonic acid turnover in the unanesthetized rat. These results are consistent with the hypothesis that drugs effective in treating the manic phase of bipolar disorder decrease brain arachidonic acid turnover.
Lee
Ho-Joo
HJ
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. hojoolee@mail.nih.gov
Rao
Jagadeesh S
JS
Chang
Lisa
L
Rapoport
Stanley I
SI
Bazinet
Richard P
RP
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D001714:Bipolar Disorder / Q000188:drug therapy*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D000077213:Lamotrigine; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D014227:Triazines / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D000214:Acyl Coenzyme A; D018692:Antimanic Agents; D010743:Phospholipids; D014227:Triazines; D016718:Arachidonic Acid; D005680:gamma-Aminobutyric Acid; D000077213:Lamotrigine