Effects of chronic treatment with (+)- and (-)-nicotine on nicotinic acetylcholine receptors and N-methyl-D-aspartate receptors in rat brain

Brain Res. 1994 Apr 25;644(1):32-9. doi: 10.1016/0006-8993(94)90343-3.


In this study, the effects of chronic treatment with (+)-nicotine on brain nicotinic acetylcholine receptors (nAChRs) and N-methyl-D-aspartate (NMDA) receptors, as well as on animal body weight were compared with those of chronic treatment with (-)-nicotine. Male Sprague-Dawley rats were s.c. injected with saline, (+)-nicotine (2.0 mg free base/kg b.w.) or (-)-nicotine (0.45 mg free base/kg b.w.) for 18 days. Brain nAChRs were investigated by (-)-[3H]nicotine binding. A significant increase in the high-affinity (-)-[3H]nicotine (5 nM)-binding sites was observed in the cortex, hippocampus, midbrain and striatum but not in the cerebellum of the rats treated with either (+)- or (-)-nicotine. The displacement curves of (-)-[3H]nicotine/(-)-nicotine in the cortices of rats treated with either (+)- or (-)-nicotine showed only one population of high-affinity binding sites, whereas both high- and low-affinity binding sites were observed in the cortices of control animals. Brain NMDA receptors were studied by [3H]MK-801, which binds to the NMDA receptor-ion channel complex. A significant decrease in the Bmax, but not in the KD for [3H]MK-801 binding in the cortices of rats treated with either (+)- or (-)-nicotine was only detected under certain experimental conditions where the NMDA receptors seem not to be maximally activated. The body weight of the animals treated with (-)-nicotine was significantly lower than that of the control animals, whereas there was no difference in body weight between (+)-nicotine- and saline-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Body Weight / drug effects
  • Brain / metabolism*
  • Dizocilpine Maleate / metabolism
  • Male
  • Nicotine / chemistry
  • Nicotine / metabolism
  • Nicotine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, Nicotinic / drug effects*
  • Stereoisomerism
  • Time Factors


  • Amino Acids
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Nicotinic
  • Dizocilpine Maleate
  • Nicotine