Acta Neurologica Belgica

, Volume 113, Issue 3, pp 319–325 | Cite as

Blunted endogenous GABA-mediated inhibition in the hypothalamic paraventricular nucleus of rats with streptozotocin-induced diabetes

  • Zurina Hassan
  • Munavvar Zubaid Abdul Sattar
  • Farah Wahida Suhaimi
  • Nurul Hasnida Mohammed Yusoff
  • Mohammed H. Abdulla
  • Ahmad Pauzi M. Yusof
  • Edward J. Johns
Original Article


The hypothalamic paraventricular nucleus (PVN) is involved in the regulation of sympathetic outflow and particularly affects the heart. This study sets out to determine the role of GABA of the paraventricular nucleus (PVN) in cardiovascular regulation in streptozotocin-induced diabetic rats. Pharmacological stimulation of glutamatergic receptors with DL-Homocysteic acid (200 mM in 100 nL) in the PVN region showed a significant depression in both mean arterial pressure (MAP) and heart rate (HR) of diabetic rats (Diabetic vs. non-diabetic: MAP 15.0 ± 1.5 vs. 35.8 ± 2.8 mmHg; HR 3.0 ± 2.0 vs. 30.0 ± 6.0 bpm, P < 0.05). Microinjection of bicuculline methiodide (1 mM in 100 nL), a GABAA receptor antagonist, produced an increase in baseline MAP and HR in both non-diabetic and diabetic rats. In the diabetic rats, bicuculline injection into the PVN reduced the pressor and HR responses (Diabetic vs. non-diabetic: MAP 6.2 ± 0.8 vs. 25.1 ± 2.2 mmHg; HR 1.8 ± 1.1 vs. 25.4 ± 6.2 bpm, P < 0.05). A microinjection of muscimol (2 mM in 100 nL), which is a GABAA receptor agonist, in the PVN elicited decreases in MAP and HR in both groups. The diabetic group showed a significantly blunted reduction in HR, but not MAP (Diabetic vs. non-diabetic: MAP −15.7 ± 4.0 vs. −25.0 ± 3.8 mmHg; HR −5.2 ± 2.1 vs. −39.1 ± 7.9 bpm). The blunted vasopressor and tachycardic responses to bicuculline microinjection in the diabetic rats are likely to result from decreased GABAergic inputs, attenuated release of endogenous GABA or alterations in GABAA receptors within the PVN.


GABAA receptors Bicuculline methiodide Muscimol Paraventricular nucleus STZ-induced diabetic rats 



This research was supported financially by Research University Grant (1001/PFARMASI/811053) from Universiti Sains Malaysia.


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Copyright information

© Belgian Neurological Society 2012

Authors and Affiliations

  • Zurina Hassan
    • 1
    • 2
  • Munavvar Zubaid Abdul Sattar
    • 2
  • Farah Wahida Suhaimi
    • 1
  • Nurul Hasnida Mohammed Yusoff
    • 1
  • Mohammed H. Abdulla
    • 4
  • Ahmad Pauzi M. Yusof
    • 3
  • Edward J. Johns
    • 4
  1. 1.Centre for Drug ResearchUniversiti Sains MalaysiaGeorgetownMalaysia
  2. 2.Department of PhysiologySchool of Pharmaceutical Sciences, Universiti Sains MalaysiaGeorgetownMalaysia
  3. 3.College of Health SciencesMasterskill UniversityCherasMalaysia
  4. 4.Department of PhysiologyUniversity College CorkCorkIreland

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