Dissociating anorexia and anhedonia elicited by interleukin-1beta: antidepressant and gender effects on responding for "free chow" and "earned" sucrose intake.
BACKGROUND
Cytokines, signaling molecules of the immune system, have been implicated in the provocation of depression. Analysis of the behavioral effects of interleukin-1beta (IL-1beta), and their modification by antidepressants, is complicated since the anorexic and anhedonic effects of the cytokine are not readily dissociated from one another.


OBJECTIVE
The effects of IL-1beta in male and female rats were evaluated with respect to free consumption of lab chow and responding for sucrose reward on a progressive ratio (PR) schedule. This schedule assesses motivation to respond by progressively increasing the efforts rats must expend to receive a fixed reward. Using this schedule, it was then possible to assess the influence of chronic fluoxetine in attenuating the effects of IL-1beta.


METHODS
The effect of a single intraperitoneal injection of IL-1beta treatment was assessed in rats trained to respond on a PR schedule for sucrose reward, and who could obtain ad lib chow. In a second experiment rats were pretreated chronically with fluoxetine by gavage for 30 days, after which the effects of IL-1beta were assessed.


RESULTS
A single intraperitoneal injection of IL-1beta reduced chow consumption for 48 h in both males and females; in contrast, among males, the effort expended to gain sucrose reward was reduced for 24 h, while in females the effect persisted for 72 h. Chronic pretreatment with fluoxetine attenuated the disturbance of PR performance elicited by IL-1beta, but did not alter the reduced chow consumption.


CONCLUSIONS
It is suggested that (a). the anhedonic and anorexic effects of IL-1beta are dissociable, (b). the cytokine disturbs incentive motivation, and (c). antidepressant treatment preferentially influences the anhedonic effects elicited by IL-1beta.
Merali
Zul
Z
Institute of Mental Health Research, Royal Ottawa Hospital, Ottawa, Canada.
Brennan
Kelly
K
Brau
Patricia
P
Anisman
Hymie
H
D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000188:drug therapy*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003216:Conditioning, Operant / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012201:Reward; D012653:Self Stimulation; D012737:Sex Factors; D013395:Sucrose / Q000008:administration & dosage
D000928:Antidepressive Agents; D007375:Interleukin-1; D005473:Fluoxetine; D013395:Sucrose