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 ωg) and water consumption was quantified. MCC produced a dose-related, transient increase in water consumption that peaked at a dose of 30 ωg. 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-β-erythriodine (DHBE), hexamethonium, and mecamylamine. However, pretreatment with the muscarinic antagonist atropine (0.01 or 1.0 ωg) 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.
|Number of pages||6|
|Journal||Pharmacology Biochemistry and Behavior|
|State||Published - Sep 1994|
Bibliographical noteFunding Information:
These studies were supported by DA-08443 (J.R.P.), the Callaway Foundation and the Department of Veterans Affairs Medical Center, Medical Research Service (J.B.B.). The procedures used in these studies conform to animal use guidelines defined by the National Institute of Health and were approved by a local animal care and utilization committee.
- Drinking behavior
ASJC Scopus subject areas
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience