N-METHYL-D-ASPARTATE INCREASES ACETYLCHOLINE-RELEASE FROM RAT STRIATUM AND CORTEX - ITS EFFECT IS AUGMENTED BY CHOLINE


ULUS I., BUYUKUYSAL R. L. , WURTMAN R.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol.261, no.3, pp.1122-1128, 1992 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 261 Issue: 3
  • Publication Date: 1992
  • Title of Journal : JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
  • Page Numbers: pp.1122-1128

Abstract

We examined the effects of N-methyl-D-aspartate (NMDA), a glutamate agonist, and of glutamate itself, on acetylcholine (ACh) release from superfused rat striatal slices. In a Mg++-free medium, NMDA (32-1000-mu-M) as well as glutamate (1 mM) increased basal ACh release by 35 to 100% (all indicated differences, P < .05), without altering tissue ACh or choline contents. This augmentation was blocked by Mg++ (1.2 mM) or by MK-801 (10-mu-M). Electrical stimulation (15 Hz, 75 mA) increased ACh release 9-fold (from 400 to 3660 pmol/mg of protein): this was enhanced (to 4850 pmol/mg of protein) by NMDA (100-mu-M). ACh levels in stimulated slices fell by 50 or 65% depending on the absence or presence of NMDA. The addition of choline (40-mu-M) increased ACh release both basally (570 pmol/mg of protein) and with electrical stimulation (6900 pmol/mg of protein). In stimulated slices choline acted synergistically with NMDA, raising ACh release to 10,520 pmol/mg of protein. The presence of choline also blocked the fall in tissue ACh. No treatment affected tissue phospholipid or protein levels. NMDA (32-320-mu-M) also augmented basal ACh release from cortical but not hippocampal slices. Choline efflux from striatal and cortical (but not hippocampal) slices decreased by 34 to 50% in Mg++-free medium. These data indicate that NMDA-like drugs may be useful, particularly in combination with choline, to enhance striatal and cortical cholinergic activity. ACh release from rat hippocampus apparently is not affected by NMDA receptors.