Corticosterone-attenuating and anxiolytic properties of mecamylamine in the rat

1. The available evidence suggests that stress induced release of acetylcho line (ACh) in the brain has a significant role in mediating neuroendocrine, emotional, and physiological responses to stress. Recent findings also sug gest that stress indirectly (via acetylcholine) and nicotine directly stimu lates the HPA axis through activation of nAChRs. 2. Our working hypothesis is that under stressful conditions, nicotinic rec eptor antagonists, such as mecamylamine, should act to attenuate the activa tion of the HPA axis and exhibit anxiolytic behavioral effects. The purpose of this study was to determine whether or not mecamylamine would: a) produ ce anxiolytic effects in rats on the elevated plus maze and b) blunt the pl asma corticosterone response to predator stress in rats. 3. Results suggested that mecamylamine has anxiolytic properties under stre ssful conditions. In the EPM experiment, mecamylamine (0.3 mg/kg) produced increased time spent in the open arms. Similarly, in the predator stressor experiment, mecamylamine blunted the stress-induced plasma corticosterone r esponse, with the lowest dose of mecamylamine (0.1 mg/kg). 4. These findings may have important therapeutic implications since clinica l observations have shown that low doses of mecamylamine reduce tension and anxiety in patients with Tourette syndrome.