Chronic stress supersensitizes rats to the inhibition of locomotion produced by arecoline

Abstract

Chronic inescapable footshock and swim stress supersensitize a hypothalamic muscarinic mechanism which regulates core body temperature. We studied the inhibitory effects of arecoline, a muscarinic agonist, on locomotion in rats before and after chronic swim stress in order to examine the effects of stress on an extra-hypothalamic muscarinic mechanism. We counted crossings in an open field during the days before and after six days of twice-daily swim stress (8 minutes/session at 12C). We first examined the effects of eight doses of ip arecoline (0.01 to 2.0 mg/kg) and normal saline (N = 6 to 8 rats/group) on crossings before and after chronic stress. Doses greater than 0.25 mg/kg inhibited pre-stress crossings relative to saline and did not potentiate the inhibition of locomotion post-stress. The 0.125 mg/kg dose reduced crossings post-stress relative to saline. We reexamined the effects of the 0.125 mg/kg dose saline (N = 20 rats/group) on crossings before and after six days of swim stress. Chronic stress potentiated arecoline-induced inhibition of locomotion. Our results suggest that chronic uncontrollable stressors may supersensitize an extra-hypothalamic muscarinic mechanism involved in the stress response and the pathophysiology of stress-related disease such as major depression.