Interleukin-2 decreases accumbal dopamine efflux and responding for rewarding lateral hypothalamic stimulation

Hymie Anisman, L. Kokkinidis, Z. Merali

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74 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalBrain Research
Issue number1-2
Publication statusPublished - 26 Aug 1996
Externally publishedYes


  • Cytokine
  • Dopamine
  • Interleukin-2
  • Intracranial self-stimulation
  • Microdialysis
  • Psychoneuroimmunology


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