Effects of lithium and purinergic compounds on the behavioral and physiological aspects of restraint stress in rats

Abstract This study investigates the effects of lithium and caffeine on psychomotor activities, defecation, and gastric lesions induced by restraint stress. Rats exposed to restraint stress typically exhibited a biphasic response consisting of an initial hypermotility (such as tail-flipping, body-rolling, jaw movement, and vocalization) accompanied by defecation, and followed by hypomotility (decrease in motility) accompanied by gastric ulceration. Lithium chloride (150 μg, ICV; 50 and 100 mg/kg, IP) significantly attenuated these responses while N 6 -cyclohexyl adenosine (CHA; 1.5 μg, ICV; 0.3 mg/kg, IP), a potent adenosine A 1 receptor agonist, attenuated the behavioral effects but potentiated the gastic ulceration. Caffeine (3 μg, ICV; 1.0 mg/kg, IP), an adenosine receptor antagonist, inhibited the effects of CHA in animals exposed to 3 h of stress, but aggravated the effects in animals exposed to 6–12 h of stress. These results suggest that caffeine consumption may produce supersensitivity of adenosine receptors, which potentiate the actions of adenosine or CHA. Lithium may modulate the effects of stress by indirectly inhibiting central adenosine receptor activity.