The excitatory amino acid L-glutamate (GLU) is known to increase the release of both 3H-acetylcholine (ACh) and 3H-dopamine (DA) from superfused rat striatal slices. N-methyl-D-aspartate (NMDA), the prototypic agonist at one of the glutamate receptor subclasses, evokes the release of DA and ACh via a mechanism which can be antagonized by phencyclidine (PCP). NMDA-evoked ACh release is reduced 80% by 1.2 mM MgCl2 while DA release is 50% reduced. In Ca+2-free buffer, NMDA-evoked ACh release is depressed to baseline levels while DA release is not. Tetrodotoxin (TTX) blocks NMDA-evoked ACh release, indicative of a somatic site of action. NMDA-induced DA release is insensitive to TTX, consistent with an action on striatal DA terminals. Other drugs with PCP-like activity inhibit NMDA-evoked striatal ACh and DA release with a rank-order potency and stereoselectivity similar to their rank-order potency in affecting several behavioral measures. These agents were approximately 10-fold more potent as antagonists of ACh release than DA release. The log-dose response curve of NMDA-induced ACh release was shifted 5-fold to the right in a non-parallel manner by 0.1 μM PCP. PCP (1 μM) was able to antagonize ACh release evoked by 1 mM GLU but was ineffective against that induced by equal concentrations of kainate and quisqualate, antagonists for other glutamate receptor subtypes.
|Original language||English (US)|
|State||Published - 1985|
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