Chronic treatment with amitriptyline produces subsensitivity to the hypothermic effects of clonidine

1. Supersensitivity or up-regulation of presynaptic alpha 2-adrenoceptors may be involved in the pathogenesis of depression. 2. The authors used a thermoregulation paradigm to test the hypothesis that chronic treatment with a tricyclic antidepressant amitriptyline (AMI) produces subsensitivity to the hypothermic effects of the alpha 2 agonist clonidine. 3. Treatment with amitriptyline produced blunting of the hypothermic response to clonidine. 4. Subsensitivity persisted for at least 21 days--that point after the discontinuation of the tricyclic at which the animals were last challenged with clonidine. 5. These findings are consistent with previous reports that tricyclic antidepressants produce subsensitivity of alpha 2 adrenoceptors.