1. The available evidence suggests that stress induced release of
acetylcholine (ACh) in the brain has a significant role in mediating neuroendocrine, emotional, and physiological responses to stress. Recent findings also suggest that stress indirectly (via
acetylcholine) and
nicotine directly stimulates the HPA axis through activation of nAChRs. 2. Our working hypothesis is that under stressful conditions,
nicotinic receptor antagonists, such as
mecamylamine, should act to attenuate the activation of the HPA axis and exhibit
anxiolytic behavioral effects. The purpose of this study was to determine whether or not
mecamylamine would: a) produce
anxiolytic effects in rats on the elevated plus maze and b) blunt the plasma
corticosterone response to predator stress in rats. 3. Results suggested that
mecamylamine has
anxiolytic properties under stressful 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 response, with the lowest dose of
mecamylamine (0.1 mg/kg). 4. These findings may have important therapeutic implications since clinical observations have shown that low doses of
mecamylamine reduce tension and anxiety in patients with
Tourette syndrome.