Stress-induced immobility in rats with cholinergic supersensitivity

Immobility during forced swimming or after mild footshock (1 mA for 2 sec) was observed in five groups of rats. The Flinders Sensitive Line (FSL) of rats, known to be more sensitive to cholinergic agonists, exhibited the greatest degree of immobility in the forced swim test. Rats chronically treated with, and subsequently withdrawn from, either scopolamine (2 mg/kg, once daily) or amitriptyline (10 mg/kg, once daily) were also significantly more immobile than either a control group treated chronically with isotonic saline or the Flinders Resistant Line (FRL) of rats in the forced swim test. Similar trends were observed for locomotor depression in the open field following exposure to footshock. Receptor binding studies indicated significantly greater concentrations of muscarinic acetylcholine receptors in the hippocampus of the scopolamine, and amitriptyline, withdrawn rats. These findings indicate that rats with increased cholinergic sensitivity are more sensitive to the immobility-inducing effects of mild stressors. Thus, they may prove to be useful models for studying the relationship between affective disorders and the cholinergic system.