Chronic clozapine reduces rat brain arachidonic acid metabolism by reducing plasma arachidonic acid availability
Year: 2012
Type: article
Abstract: Chronic administration of mood stabilizers to rats down-regulates the brain arachidonic acid (AA) cascade. This down-regulation may explain their efficacy against bipolar disorder (BD), in which brain AA cascade markers are elevated. The atypical antipsychotics, olanzapine (OLZ) and clozapine (CLZ), also act against BD. When given to rats, both reduce brain cyclooxygenase activity and prostaglandin E(2) concentration; OLZ also reduces rat plasma unesterified and esterified AA concentrations, and AA incorporation and turnover in brain phospholipid. To test whether CLZ produces similar changes, we used our in vivo fatty acid method in rats given 10 mg/kg/day i.p. CLZ, or vehicle, for 30 days; or 1 day after CLZ washout. [1-(14) C]AA was infused intravenously for 5 min, arterial plasma was collected and high-energy microwaved brain was analyzed. CLZ increased incorporation coefficients ki * and decreased [corrected] rates J(in,i) of plasma unesterified AA into brain phospholipids. [corrected]. These effects disappeared after washout. Thus, CLZ and OLZ similarly down-regulated kinetics and cyclooxygenase expression of the brain AA cascade, likely by reducing plasma unesterified AA availability. Atypical antipsychotics and mood stabilizers may be therapeutic in BD by down-regulating, indirectly or directly respectively, the elevated brain AA cascade of that disease.
Source: Journal of Neurochemistry
DOI: 10.1111/jnc.12078
Institutions: National Institutes of Health, National Institute on Aging
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
Award: G9000254024
OpenAlex ID: W1992883552