Interleukin-2 modulates N-methyl-D-aspartate receptors of native mesolimbic neurons

Jiang Hong Ye, Liang Tao, Steven S. Zalcman

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Interleukin (IL)-2 is a brain-derived cytokine that influences mesocorticolimbic dopamine release, and is associated with pathological outcomes that are mediated, at least in part, by aberrations in mesolimbic neurotransmission. The mechanisms by which IL-2 modulates mesolimbic transmission, however, are not known. The NMDA receptor/channel (NMDAR) plays an essential role in neuronal excitability of mesolimbic neurons; we thus examined in neonatal rats the effects of IL-2 on NMDA-activated current (INMDA) in voltage-clamped neurons freshly isolated from the ventral tegmental area (VTA), the site of origin of the mesolimbic system. IL-2 (0.01-500 ng/ml) alone had no effect on membrane conductance. When co-applied with NMDA, IL-2 (50-500 ng/ml) significantly potentiated INMDA. In contrast, doses as low as 0.01 ng/ml markedly decreased the NMDA response. Dose-response analysis showed that IL-2 (>50 ng/ml) increased the maximal INMDA, without changing the EC50, indicating that IL-2 potentiates INMDA by increasing the efficacy of the NMDAR. Moreover, current-voltage analysis revealed that IL-2 potentiation of INMDA was voltage-dependent, being greater at negative potentials. In contrast, IL-2 inhibition of INMDA was voltage-independent, and IL-2 did not alter the reversal potential. Additionally, IL-2 (1 ng/ml) shifted the NMDA concentration-response curve to the right, significantly increasing the EC50 for NMDA without changing the maximal INMDA, suggesting that IL-2 inhibits the NMDAR by a competitive mechanism. IL-2 thus acts as a potent modulator of the NMDAR. IL-2-induced alterations of responses to NMDAR activation may contribute to synaptic plasticity in the mesolimbic system and to pathological outcomes associated with this system.

Original languageEnglish (US)
Pages (from-to)241-248
Number of pages8
JournalBrain research
Issue number2
StatePublished - Mar 16 2001

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


  • Cytokine
  • Development
  • Dopamine
  • Excitatory amino acid
  • Patch clamp
  • Ventral tegmental area


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