Effects of muscarinic receptor agonists and antagonists on swim-stress-induced 'behavioural despair' in rats

The effects of some selective agonists and antagonists of cholinergic muscarinic receptor subtypes on swim-stress-induced immobility (SI) was investigated in rats. This paradigm has been proposed to assess 'behavioural despair' in rodents as a laboratory model for clinical depression. All the rats were pre-treated with atropine ethoiodide i.p. to obviate any peripheral cholinergic influence. SI was only marginally less in intracerebroventricular (i.c.v.) cannulated rats administered artificial cerebrospinal fluid than in uncan nulated rats administered normal saline i.p. The drugs which do not have access across the blood-brain barrier were administered i.c.v. The muscarinic M₁ receptor agonists, arecholine and McN-A-343, and the non-specific muscarinic receptor agonist, oxotremorine, induced dose-related increases in SI, whereas the muscarinic M₁ receptor antagonists, scopolamine and pirenzepine, and the non-specific antagonist, atropine, produced significant decreases in SI. Carbachol, an M₂ receptor agonist, and physostigmine induced a dose- dependent dual effect, with lower doses attenuating and higher doses augmenting SI. The M₂ receptor antagonists, gallamine and AF-DX 116, increased SI. The data may be interpreted to suggest that muscarinic M₁ receptors may function to accentuate depression whereas muscarinic M₂ receptors may exert an inhibitory modulatory effect.