title: The non-steroidal anti-inflammatory drug diclofenac sodium attenuates lipopolysaccharide-induced alterations to reward behavior and corticosterone release.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to counteract stress hormone and pro-inflammatory cytokine activation. To extend these findings, we tested whether the NSAID diclofenac sodium would attenuate lipopolysaccharide (LPS)-induced reductions in reward behavior. In the first experiment, male, Wistar rats pressed a lever for food reward and subsequently received 10 days treatment of saline (1 ml/kg, s.c.) or diclofenac (2.5mg/kg, s.c.). On the subsequent test day, rats were given a final injection of saline or diclofenac 30 min prior to LPS (20 micrograms/kg, i.p.). LPS significantly reduced rate of food self-administration and total reinforcers obtained and increased corticosterone levels in saline-treated rats, while these effects were significantly attenuated in diclofenac-treated rats. In the second experiment, rats pressed a lever for sweetened milk. In contrast to food self-administration, acute LPS exposure did not reduce rate of responding or total reinforcers obtained in either saline- or diclofenac-treated rats. In the third experiment, rats trained to press a lever for sweetened milk were pre-exposed to a high dose of LPS (250 micrograms/kg, i.p.) 2 weeks prior to a challenge injection of LPS. In this case, LPS challenge significantly reduced rate of sweetened milk self-administration, but not total reinforcers obtained, in saline-treated rats. Rats treated with diclofenac did not exhibit reductions in rate of responding or total reinforcers obtained. Overall, the data indicate that the NSAID diclofenac sodium counteracts LPS-induced reductions in reward behavior and corticosterone release, and may therefore have therapeutic potential for specific components of endotoxin-induced sickness behavior, including anhedonia.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Forchheimer Building, Room 111, 1300 Morris Park Avenue, Bronx, NY 10461, USA. rdelagar@aecom.yu.edu
authors.forename: Richard
authors.initials: R
authors.lastname: De La Garza
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Fabrizio
authors.forename: Gina Elena
authors.initials: GE
authors.lastname: Radoi
authors.forename: Tudor
authors.initials: T
authors.lastname: Vlad
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Asnis
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D009042:Motivation; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012653:Self Stimulation / Q000187:drug effects; D013312:Stress, Physiological / Q000503:physiopathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D004008:Diclofenac; D003345:Corticosterone