PHARMACOLOGICAL EVALUATION OF METHYLCARBAMYLCHOLINE-INDUCED DRINKING BEHAVIOR IN RATS

Methylcarbamylcholine (MCC), a structural analog of carbachol (an acet ylcholine agonist), has been reported to be a specific nicotinic choli nergic receptor ligand. MCC produces a robust polydipsic response shor tly following central administration. The purpose of the present study was to pharmacologically characterize this increase in drinking behav ior. Male Wistar rats were implanted with intracerebroventricular (ICV ) cannula guides directed at the left lateral ventricle. Following a r ecovery period, animals were injected ICV with saline or various doses of MCC (3-60 mu g) and water consumption was quantified. MCC produced a dose-related, transient increase in water consumption that peaked a t a dose of 30 mu g. In contrast, nicotine, a potent nicotinic choline rgic receptor agonist, did not produce changes in drinking following I CV administration. MCC-induced increases in drinking were not blocked by pretreatment with several selective nicotinic receptor antagonists including dihydro-beta-erythriodine (DHBE), hexamethonium, and mecamyl amine. However, pretreatment with the muscarinic antagonist atropine ( 0.01 or 1.0 mu g) completely abolished MCC-induced polydipsia. Followi ng a chronic treatment regimen (MCC injected ICV twice daily for 10 da ys), no tolerance to MCC-induced changes in water consumption was obse rved. Previous studies have demonstrated that tolerance develops to ni cotinic-receptor mediated responses following the identical chronic tr eatment paradigm. These results suggest that MCC-induced polydipsia is mediated through stimulation of muscarinic rather than nicotinic rece ptors.