Garza et al's Acute Diclofenac Treatment Attenuates Lipopolysaccharide-induced Alternations to Basic

Garza et al's Acute Diclofenac Treatment Attenuates Lipopolysaccharide-induced Alternations to Basic

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Psychopharmacology (2005) 179: 356 365 DOI 10.1007/s00213-004-2053-x ORIGINAL INVESTIGATION Richard De La Garza II . Gregory M. Asnis . Kevin R. Fabrizio . Erika Pedrosa Acute diclofenac treatment attenuates lipopolysaccharide-induced alterations to basic reward behavior and HPA axis activation in rats Received: 3 February 2004 / Accepted: 23 September 2004 / Published online: 25 November 2004 # Springer-Verlag 2004 Abstract Rationale: Non-steroidal anti-inflammatory drugs (NSAIDs) counteract stress hormone and pro-inflammatory cytokine activation, and are being considered as therapeu- tics for Alzheimer s and Parkinson s disease, and multiple sclerosis. Previous data from our laboratory revealed that repeated treatment with the NSAID diclofenac attenuated lipopolysaccharide (LPS)-induced alterations to reward behavior, implicating a role for NSAIDs in alleviating de- pressive-like behavior. Objectives: To extend these find- ings, we sought to determine whether acute treatment with diclofenac would attenuate LPS-induced alterations to basic reward behavior, as well as neuroendocrine and neuroim- mune function. Methods: Male, Wistar rats ( n =8 9/grp) pressed a lever for sucrose pellet reward and after estab- lishing a steady baseline were exposed to an injection of saline (1 ml/kg, SC) or diclofenac (2.5 mg/kg, SC) 30 min prior to a second injection of saline or LPS (20 μ g/kg, IP). Results: In saline pre-treated rats, LPS significantly re- duced rate of sucrose pellet self-administration and total reinforcers obtained, suggestive of an anhedonia response. In addition, LPS increased corticosterone release, increased plasma intereleukin (IL)-1 β release, increased IL-1 β and IL-6 mRNA in hippocampus, increased corticotropin re- leasing hormone (CRH) mRNA in pituitary, and decreased CRH-1 mRNA in pituitary. Importantly, the behavioral and neuroendocrine effects, but not neuroimmune effects, produced by LPS were significantly attenuated in rats pre- treated with diclofenac. Conclusions: These new data pro- vide a comprehensive assessment of the acute effects of diclofenac on LPS exposure in rats and confirm a role for NSAIDs in attenuating endotoxin-induced anhedonia. Of particular importance, the data reveal that the observed effects are mediated via the hypothalamic pituitary adrenal axis at the level of the pituitary or above. Keywords NSAID . Anhedonia . Depression . Lipopolysachharide . Endotoxin . Corticosterone . Diclofenac . IL-1 β . IL-6 . CRH . CRH-1 Introduction In humans, neuroendocrine and neuroimmune activation induces a number of neuropsychological symptoms, col- lectively referred to as flu-like syndrome , and consists of anhedonia, anorexia, fever, fatigue, increased pain, sleep disturbances, and confusion (Licinio et al. 1998 ; Konsman et al. 2002 ). A close linkage between flu-like syndrome and major depressive disorder (MDD) in humans has been pre- dicted to arise due to hypersecretion of pro-inflammatory
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This note was uploaded on 04/13/2010 for the course PSYCH 101 taught by Professor Gabbart during the Spring '08 term at Union College.

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Garza et al's Acute Diclofenac Treatment Attenuates Lipopolysaccharide-induced Alternations to Basic

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