Assessment of the muscarinic receptor subtype involved in the mediation of pilocarpine-induced purposeless chewing behaviour

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Abstract
Purposeless chewing behaviour in rats was enhanced by intraperitoneal administration of the muscarinic agonists pilocarpine (1.0–8.0 mg/kg). RS 86 (0.5–0.8 mg/kg), oxotremorine (1–2 mg/kg) and arecoline (2–32 mg/kg), but not by nicotine (0.1–3.2 mg/kg). Chewing behaviour was also induced by the ICV administration of the muscarinic agonists carbachol (12.5–100 μg) and pilocarpine (50–200 μg), but not by the putative M-1 receptor agonist McN-A-343 (50–200 μg) or AH 6405 (100–200 μg). The muscarinic receptor antagonists scopolamine (0.01–0.1 mg/kg SC), benzhexol (0.075–2.5 mg/kg SC), secoverine (1–10 mg/kg SC), and dicyclomine (1.25–10 mg/kg SC) antagonised purposeless chewing behaviour induced by pilocarpine (4 mg/kg IP). AF-DX 116 (2.5–100 mg/kg SC), an M-2 antagonist, partially inhibited the actions of pilocarpine (4 mg/kg IP). Based on ED40 values the rank order of potency following IP administration was scopolamine > benzhexol > secoverine > dicyclomine > AF-DX 116. The ICV administration of the muscarinic antagonists N-methylscopolamine (2.5–10 μg) and oxyphenonium (10–40 μg) antagonised chewing behaviour induced by pilocarpine (4 mg/kg IP) in a dose-related manner. The M-2 antagonist 4-DAMP (40–160 μg ICV), as well as AF-DX 116 (40–160 μg ICV), also inhibited the effects of pilocarpine (40–160 μg ICV). The putative M-1 receptor antagonist pirenzepine (80–320 μg ICV) did not antagonise chewing behaviour induced by pilocarpine (4 mg/kg IP). Based on ED40 values, the rank order of potency of muscarinic antagonists administered ICV was N-methylscopolamine > oxyphenonium > 4-DAMP > AF-DX 116 > pirenzepine. Comparisons of the actions of muscarinic antagonists in vivo, with their published actions in vitro suggest that pilocarpine-induced chewing behaviour is mediated through central M-2 receptors rather than via central M-1 sites.