M2 Muscarinic Autoreceptors Modulate Acetylcholine Release in the Medial Pontine Reticular Formation

Muscarinic autoreceptors regulate acetylcholine (ACh) release in several brain regions, including the medial pontine reticular formation (mPRF). This study tested the hypothesis that the muscarinic cholinergic receptor mediating mPRF ACh release is the pharmacologically defined M2 subtype. In vivo microdialysis was used to deliver muscarinic cholinergic receptor (MAChR) antagonists to the feline mPRF while simultaneously measuring endogenously released ACh. The lowest concentration of each antagonist that caused a significant increase in mPRF ACh release was determined and defined as the minimum ACh-releasing concentration. Data obtained from 41 mPRF dialysis sites in 10 animals showed that the order of potency (followed by the minimum ACh-releasing concentration) was scopolamine (1 nM) > AF-DX 116 (3 nM) > pirenzepine (300 nM). Comparison of these minimum ACh-releasing concentrations to the known affinities of the antagonists for the five mAChR subtypes is consistent with the conclusion that the autoreceptor regulating mPRF ACh release is the M2 subtype. Considerable evidence supports a role for cholinergic neurotransmission and postsynaptic M2 receptors in the mPRF in regulating levels of arousal. The present data suggest that presynaptic M2 receptors contribute to the regulation of arousal states by modulating mPRF ACh release.