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

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 micrograms) and pilocarpine (50-200 micrograms), but not by the putative M-1 receptor agonist McN-A-343 (50-200 micrograms) or AH 6405 (100-200 micrograms). 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 greater than benzhexol greater than secoverine greater than dicyclomine greater than AF-DX 116. The ICV administration of the muscarinic antagonists N-methylscopolamine (2.5-10 micrograms) and oxyphenonium (10-40 micrograms) antagonised chewing behaviour induced by pilocarpine (4 mg/kg IP) in a dose-related manner. The M-2 antagonist 4-DAMP (40-160 micrograms ICV), as well as AF-DX 116 (40-160 micrograms ICV), also inhibited the effects of pilocarpine (40-160 micrograms ICV). The putative M-1 receptor antagonist pirenzepine (80-320 micrograms ICV) did not antagonise chewing behaviour induced by pilocarpine (4 mg/kg IP).(ABSTRACT TRUNCATED AT 250 WORDS)

Motor effects of GABA A antagonism in globus pallidus: studies of locomotion and tremulous jaw movements in rats

“…The fact that bicuculline injected into the GP did not reduce pilocarpine-induced jaw movements is consistent with the notion that striatal M4 muscarinic receptors, which are localized more densely on striatonigral as opposed to striatopallidal neurons (Hersch and Levey 1995;Santiago and Potter 2001), are involved in the production of the jaw movements induced by muscarinic agonists (Mayorga et al 1999b;Salamone et al 2001). In contrast, M1 muscarinic receptors, which are expressed on both striatopallidal and striatonigral neurons, appear to be less involved in pilocarpine-induced tremulous jaw movements (Stewart et al 1989;Mayorga et al 1999b;Salamone et al 2001). Although pilocarpine-and haloperidol-induced jaw movements appear to have some different pharmacological characteristics, this does not mean that cholinomimetic-induced jaw movements are unrelated to parkinsonism.…”

Nicotine-induced purposeless chewing in rats: possible dopamine receptor mediation

“…The chewing induced was vacuous chewing movements, as have been described by Waddington (1990). The data is not in agreement with that obtained by Stewart, Jenner and Marsden (1989) who could not find any response for nicotine. The failure of nicotine to induce chewing in their study may be due to the high doses of drug used by the authors.…”

“…Chewing may be produced by a central cholinergic mechanism (Collins et al, 1989;Stewart, Jenner and Marsden, 1989;Zarrindast et al, 1992). Dopamine D-1 and D-2 receptors also have been shown to produce opposing or independent effects on cholinergic neurones in the striatum (Fage and Scatton, 1986;Gorell, Czarnecki and Hubbell, 1986;Consolo, Wu and Fusi, 1987).…”

“…Different muscarinic receptor subtypes have been shown (Hammer and Giachetti, 1982;Hammer et al, 1986). The chewing behaviour has been proposed to be mediated through central M2 receptors rather than via central M 1 sites (Stewart, Jenner and Marsden, 1989).…”

Roles of .Mu.-Opioid Receptors in Development of Tolerance to Diisopropylfluorophosphate (Dfp)

“…These results may be associated with the regulation of behaviors by specific muscarinic receptor subtypes. For example, tremors are related to M2 muscarinic receptors ) and chewing movements are related to M4 muscarinic receptors (Stewart et al, 1989). There was compensatory downregulation of M2 muscarinic receptors in µ-opioid Hippocampal formation 0.09 ± 0.002 0.08 ± 0.002 0.13 ± 0.001 0.09 ± 0.002 0.08 ± 0.002 0.12 ± 0.001 CA1 0.08 ± 0.001 0.09 ± 0.001 0.10 ± 0.001 0.08 ± 0.001 0.08 ± 0.001 0.09 ± 0.003 CA2 0.08 ± 0.001 0.08 ± 0.001 0.09 ± 0.001 0.07 ± 0.001 0.07 ± 0.002 0.09 ± 0.002 CA3 0.08 ± 0.001 0.07 ± 0.001 0.10 ± 0.001 0.07 ± 0.002 0.08 ± 0.001 0.10 ± 0.004 Dentate gyrus Values are represented as means ± S.E.M.…”