Pharmacological evaluation of methylcarbamylcholine-induced drinking behavior in rats.
Methylcarbamylcholine (MCC), a structural analog of carbachol (an acetylcholine agonist), has been reported to be a specific nicotinic cholinergic receptor ligand. MCC produces a robust polydipsic response shortly following central administration. The purpose of the present study was to pharmacologically characterize this increase in drinking behavior. Male Wistar rats were implanted with intracerebroventricular (ICV) cannula guides directed at the left lateral ventricle. Following a recovery period, animals were injected ICV with saline or various doses of MCC (3-60 micrograms) and water consumption was quantified. MCC produced a dose-related, transient increase in water consumption that peaked at a dose of 30 micrograms. In contrast, nicotine, a potent nicotinic cholinergic receptor agonist, did not produce changes in drinking following ICV administration. MCC-induced increases in drinking were not blocked by pretreatment with several selective nicotinic receptor antagonists including dihydro-beta-erythriodine (DHBE), hexamethonium, and mecamylamine. However, pretreatment with the muscarinic antagonist atropine (0.01 or 1.0 microgram) completely abolished MCC-induced polydipsia. Following a chronic treatment regimen (MCC injected ICV twice daily for 10 days), no tolerance to MCC-induced changes in water consumption was observed. Previous studies have demonstrated that tolerance develops to nicotinic-receptor mediated responses following the identical chronic treatment paradigm. These results suggest that MCC-induced polydipsia is mediated through stimulation of muscarinic rather than nicotinic receptors.
Yang
X
X
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta.
Buccafusco
J J
JJ
Pauly
J R
JR
D000818:Animals; D002217:Carbachol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D008024:Ligands; D008297:Male; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D018678:Cholinergic Agents; D018680:Cholinergic Antagonists; D008024:Ligands; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; C053765:N-methylcarbamylcholine; D002217:Carbachol