Chronic treatment with amitriptyline produces supersensitivity to nicotine

The authors used a thermoregulation paradigm to evaluate effects of amitriptyline (AMI) on the sensitivity of a nicotinic mechanism involved in the regulation of core temperature in rats. Treatment with this tricyclic was associated with a significant increase in the hypothermic response to nicotine. Supersensitivity persisted for a minimum of 7.5 days following the last dose of AMI, and a significant proportion of animals displayed increased sensitivity after 14.5 days of abstinence. Implications for the mechanism of action of AMI are highlighted.