The effects of local perfusion with the competitive NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP-5) and the glutamate receptor agonist N-methyl-D-aspartate (NMDA) on release of extracellular acetylcholine (ACh) and choline (Ch) in the dorsolateral striatum were studied using in vivo microdialysis in freely moving rats. AP-5 caused a dose-dependent decrease in ACh release that was counteracted by the addition of NMDA. Perfusion with AP-5 also decreased Ch levels. Local perfusion with NMDA induced an elevation of ACh release in low (10(-5) M), but not high (10(-2) M and 10(-3) M) concentrations, that were associated with massive cellular death. These inhibitory effects of AP-5 and the stimulatory effect of NMDA in non-neurotoxic dosages on ACh release provide further evidence for a tonic stimulation of striatal cholinergic interneurons by glutamatergic neurons via NMDA receptors.
Muscarinic receptors (mAChRs) in the pontine reticular formation comprise a critical part of the REM sleep-generating system. Although the role of specific mAChR subtypes remains unclear, data from in vivo microinjection studies suggest that in the pons the M2 subtype is important for REM sleep generation. The present study tested the hypothesis that M2 antagonists would show a greater binding potency in feline pons than M1 or M3 antagonists. Competition binding assays showed 4-DAMP to be more potent than pirenzepine or AF-DX 116 in its ability to displace tritiated quinuclidinyl benzilate, and linear regression analyses indicated that 4-DAMP and pirenzepine each interacted with more than one binding site. These data demonstrate the presence of a mixture of mAChR subtypes in the feline pons, and are consistent with the view that REM sleep is mediated by more than one mAChR subtype.
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