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Effects of NMDA antagonist MK-801 on radial maze performance in Zucker rats

Miyuki Nishiga1, Yoko Fujii, Yukio Sugimoto

  • 1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, 700-8530, Okayama, Japan.

Brain Research
|September 17, 2002
PubMed

Insights

Obese rats show altered spatial memory, with NMDA receptor antagonists impairing performance unlike histamine blockers. This suggests NMDA receptor involvement in obese rat spatial memory.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • The NMDA receptor and histaminergic system play roles in cognitive functions, including spatial memory.
  • Zucker rats, a model for obesity and diabetes, exhibit distinct physiological and behavioral characteristics compared to lean rats.

Purpose of the Study:

  • To investigate the involvement of the N-methyl-D-aspartate (NMDA) receptor in the histaminergic system's effect on spatial memory in lean and obese Zucker rats.
  • To compare the effects of a histamine receptor antagonist (pyrilamine) and an NMDA receptor antagonist (MK-801) on radial maze performance in these rat models.

Main Methods:

  • Radial maze task was used to assess spatial memory in lean and obese Zucker rats.
  • Rats were administered pyrilamine (histamine H1 receptor antagonist) and MK-801 (NMDA receptor antagonist).
  • Performance was evaluated based on spatial memory deficits observed after drug administration.

Main Results:

  • Pyrilamine caused significant spatial memory deficits in lean rats but not in obese rats.
  • MK-801 induced significant spatial memory deficits in obese rats compared to lean rats.
  • These findings suggest a differential involvement of histaminergic and NMDA receptor systems in spatial memory between lean and obese Zucker rats.

Conclusions:

  • The histaminergic neuron system appears less involved in radial maze performance in obese rats compared to lean rats.
  • The heightened sensitivity to MK-801 in obese rats suggests increased NMDA receptor activation or a more critical role in their spatial memory.
  • This study highlights potential differences in neurotransmitter system involvement in cognitive function related to obesity.

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