The role of nitric oxide in striatal acetylcholine release induced by N-methyl-D-aspartate

Neurochem Int. 1998 Sep;33(3):255-61. doi: 10.1016/s0197-0186(98)00029-1.


Effect of nitric oxide (NO) on striatal acetylcholine (ACh) release induced by N-methyl-D-aspartate (NMDA) was investigated in freely moving rats by means of microdialysis. NMDA caused a significant increase in ACh release in the striatum, which was blocked by the specific NMDA receptor antagonists, (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), indicating that agonist-evoked increase in ACh release in the striatum was through an NMDA receptor-mediated mechanism. NG-monomethyl-L-arginine acetate salt (L-NMMA; a NO synthase inhibitor) facilitated NMDA-evoked increase in ACh release, while L-arginine (the precursor of NO) inhibited the ACh release. The increase by L-NMMA of ACh release induced by the NMDA was also blocked by L-arginine. These results suggest that NO induced by NMDA receptor-mediated mechanism in cholinergic neurons may mediate an inhibitory regulation of ACh release.

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Arginine / pharmacology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dibutyryl Cyclic GMP / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Male
  • N-Methylaspartate / pharmacology*
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroprusside / pharmacology
  • Piperazines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • omega-N-Methylarginine / pharmacology


  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • Nitroprusside
  • omega-N-Methylarginine
  • Nitric Oxide
  • Dibutyryl Cyclic GMP
  • N-Methylaspartate
  • Dizocilpine Maleate
  • Arginine
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • Nitric Oxide Synthase
  • Acetylcholine