Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in brain phospholipids: a possible common effect of mood stabilizers.
Both (Li(+)) and valproic acid (VPA) are effective in treating bipolar disorder, but the pathway by which either works, and whether it is common to both drugs, is not agreed upon. We recently reported, using an in vivo fatty acid model, that Li(+) reduces the turnover rate of the second messenger arachidonic acid (AA) by 80% in brain phospholipids of the awake rat, without changing turnover rates of docosahexaenoic or palmitic acid. Reduced AA turnover was accompanied by down-regulation of gene expression and protein levels of an AA-specific cytosolic phospholipase A(2) (cPLA(2)). To see if VPA had the same effect on AA turnover, we used our in vivo fatty acid model in rats chronically administered VPA (200 mg/kg, i.p. for 30 days). Like Li(+), VPA treatment significantly decreased AA turnover within brain phospholipids (by 28-33%), although it had no effect on cPLA(2) protein levels. Thus, both mood stabilizers, Li(+) and VPA have a common action in reducing AA turnover in brain phospholipids, albeit by different mechanisms.
Chang
M C
MC
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892-7965, USA. changm@ncrr.nih.gov
Contreras
M A
MA
Rosenberger
T A
TA
Rintala
J J
JJ
Bell
J M
JM
Rapoport
S I
SI
D000214:Acyl Coenzyme A / Q000032:analysis; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry; D005227:Fatty Acids / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008297:Male; D010741:Phospholipases A / Q000032:analysis / Q000235:genetics; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014316:Tritium; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D000214:Acyl Coenzyme A; D018692:Antimanic Agents; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D014316:Tritium; D016718:Arachidonic Acid; D014635:Valproic Acid; D008094:Lithium; D010741:Phospholipases A