Modulation of behavior and glutamate receptor mRNA expression in rats after sub-chronic administration of benzo(a)pyrene

Biomed Environ Sci. 2011 Aug;24(4):408-14. doi: 10.3967/0895-3988.2011.04.012.

Abstract

Objective: The present study aimed to test whether exposure to benzo(a)pyrene [B(a)P] affects spatial learning and short-term memory by modulating the expression of the Gria1 and Grin2a glutamate receptor subunit genes in the hippocampus.

Methods: Thirty-six 21-24-day-old, male rats were randomly assigned into high-, medium-, and low-dose toxin exposure groups (6.25, 2.5, and 1 mg/kg, respectively) and a control group, each containing nine rats. The behavioral performance of adult rats exposed to sub-chronic administration of B(a)P was monitored by learning and memory tests (Morris water maze). Real-time PCR assays were used to quantify Gria1 and Grin2a gene expression in the hippocampus.

Results: At medium and high doses, B(a)P impaired spatial learning performance. The crossing-platform-location frequency and the time spent swimming in the platform area, which both relate to short-term memory, were significantly decreased in B(a)P-treated rats compared with controls. The level of Gria1 mRNA increased 2.6-5.9-fold, and the level of Grin2a mRNA increased 10-14.5-fold, with a greater fold increase associated with higher doses of B(a)P.

Conclusion: We demonstrated that sub-chronic administration of B(a)P inhibits spatial learning and short-term memory, and increases Gria1 and Grin2a expression in the hippocampus. This suggests a relationship of B(a)P exposure levels with Gria1 and Grin2a expression and impairment of short-term and spatial memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Benzo(a)pyrene / administration & dosage
  • Benzo(a)pyrene / toxicity*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Gene Expression Regulation / drug effects*
  • Hippocampus / metabolism
  • Learning / drug effects
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Rats
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

  • RNA, Messenger
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Benzo(a)pyrene
  • glutamate receptor ionotropic, AMPA 1
  • N-methyl D-aspartate receptor subtype 2A