The non-steroidal anti-inflammatory drug diclofenac sodium attenuates IFN-alpha induced alterations to monoamine turnover in prefrontal cortex and hippocampus.
Interferon-alpha (IFN-alpha) administration induces major depression in a significant number of patients undergoing treatment for viral illnesses and other chronic diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to counteract a number of IFN-alpha-induced side effects, including pro-inflammatory cytokine activation and stress hormone release. To investigate this possibility further, we sought to determine the effect of the NSAID diclofenac sodium on monoamine turnover in brain induced by acute IFN-alpha exposure. Eleven male, Wistar rats (8 weeks old) were pretreated with diclofenac (20 mg/kg, s.c.) or saline, followed by intracerebroventricular (i.c.v.) infusion of IFN-alpha (1000 IU in 5 microl) or vehicle. The prefrontal cortex, striatum, and hippocampus were isolated and samples were assayed for monoamines and major metabolites by high-pressure liquid chromatography with electrochemical detection. The data show that acute IFN-alpha increased serotonin turnover in prefrontal cortex and increased dopamine turnover in hippocampus, while pre-treatment with diclofenac completely prevented these neurochemical responses. Importantly, these changes were recorded in two brain areas known to be important in depression and antidepressant action. These data offer support for a novel role of NSAIDs in modulating IFN-alpha-induced neurochemical alterations, and raise the possibility of the use of NSAIDs for the prevention of IFN-alpha-induced depression.
De La Garza
Richard
R
Albert Einstein College of Medicine, Department of Psychiatry and Behavioral Sciences, Forchheimer, Room 111, 1300 Morris Park Avenue, Bronx, NY 10461, USA. rdelagar@aecom.yu.edu
Asnis
Gregory M
GM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000139:chemically induced / Q000378:metabolism; D004008:Diclofenac / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015306:Biogenic Monoamines; D016898:Interferon-alpha; D004008:Diclofenac