Interleukin-2 decreases accumbal dopamine efflux and responding for rewarding lateral hypothalamic stimulation.
Systemic administration of interleukin-2 (IL-2) provoked marked alterations of responding for rewarding brain stimulation from the medial forebrain bundle (MFB). In particular, when animals were tested for ICSS immediately following IL-2 treatment only a modest disturbance of responding was evident. However, if animals were subsequently exposed to repeated daily ICSS sessions (24-168 h) in the drug-free state, rightward shifts in the rate intensity functions and significant increases in reward thresholds were apparent. These results were dependent upon the presence of IL-2 during the initial ICSS session. If animals were tested for ICSS 24 h after IL-2 administration, without an intervening test, performance was unaffected. Evaluation of nonreinforced behavior after IL-2 treatment revealed that ICSS remained under stimulus control and the cytokine did not provoke reward-unrelated performance deficits. Dopamine (DA) activity in the nucleus accumbens has been implicated in goal-directed responding to positively reinforcing stimuli and in the present investigation, using in vivo microdialysis, it was observed that IL-2 markedly reduced DA release from this region. It was suggested that the protracted consequences of IL-2 on ICSS likely do not involve motoric, soporific, attentional or cognitive changes, but may be attributable to its specific actions on motivational arousal, possibly engendered by the cytokine-induced diminution of accumbal DA efflux.
Anisman
H
H
Department of Psychology, Carleton University, Ottawa, Ont, Canada.
Kokkinidis
L
L
Merali
Z
Z
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004532:Ego; D004558:Electric Stimulation; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012653:Self Stimulation / Q000187:drug effects / Q000502:physiology
D007376:Interleukin-2; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine