Interaction between GABA and norepinephrine in interleukin-1β-induced suppression of the luteinizing hormone surge

Madhu P. Sirivelu, Robert Burnett, Andrew C. Shin, Charlotte Kim, P. S. MohanKumar, Sheba M.J. MohanKumar

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13 Scopus citations


Interleukin-1β (IL-1β), a cytokine that is closely associated with inflammation and immune stress, is known to interfere with reproductive functions. Earlier studies have demonstrated that IL-1β inhibits the luteinizing hormone (LH) surge during the afternoon of proestrus in female rats. We have shown that this effect is most probably mediated through a reduction in norepinephrine (NE) levels in the medial preoptic area (MPA) of the hypothalamus. However, the mechanism by which IL-1β decreases NE levels in the MPA is unclear. We hypothesized that the inhibitory neurotransmitter, GABA could play a role in decreasing NE levels in the MPA. To test this, ovariectomized, steroid-primed rats were injected (i.p.) with either PBS-BSA (control) or 5 μg of IL-1β, alone or in combination with i.c.v. administration of GABA-A and GABA-B receptor antagonists, Bicuculline and CGP 35348 (CGP) respectively. Animals were subjected to push-pull perfusion of the MPA and perfusates collected at 30 min intervals were analyzed for both NE and GABA levels using HPLC-EC. Simultaneously, serial plasma samples were obtained through jugular catheters and were analyzed for LH levels using RIA. Compared to control rats, NE levels decreased significantly in the MPA in IL-1β-treated rats (p < 0.05). Concurrently, there was a significant increase in GABA levels in the MPA (p < 0.05). The GABA-A receptor antagonist, bicuculline, was able to reverse the effect of IL-1β on NE and LH, while the GABA-B receptor antagonist, CGP 35348 was without any effect. This leads us to conclude that the IL-1β-induced suppression of the LH surge is most probably mediated through an increase in GABA levels in the MPA which causes a reduction in NE levels. This is probably one of the mechanisms by which IL-1β inhibits reproductive functions.

Original languageEnglish
Pages (from-to)107-114
Number of pages8
JournalBrain Research
StatePublished - Jan 12 2009


  • GABA
  • GABA antagonist
  • Interleukin-1β
  • Luteinizing hormone
  • Norepinephrine
  • Push-pull perfusion


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