Blunted temperature and cortisol responses to ipsapirone in major depression: lack of enhancement by electroconvulsive therapy

Depression has been shown in some studies to be associated with a reduction in hypothalamic 5-HT(1A) receptor function, as indicated by reduced hormone and/or hypothermic responses to 5-HT(1A) agonists such as ipsapirone. The hypothermic response to ipsapirone was reduced in depressed patients treated with amitriptyline. Hormone and hypothermic responses to 5-HT(1A) agonists were reduced in normal subjects administered specific serotonin reuptake inhibitors. Effects of electroconvulsive therapy (ECT) on 5-HT(1A) receptor-mediated responses in humans have not been reported. In the present work, ten depressed patients and 15 control subjects were challenged with placebo and with 0.3 mg/kg ipsapirone, administered 48 h apart in a randomised double blind design. Hypothermic, growth hormone (GH) and cortisol responses were measured. Seven of the depressed patients were treated with a course of ECT, and placebo and ipsapirone challenges were repeated 24 and 72 h after the last treatment. The cortisol response to ipsapirone was significantly reduced in the depressed patients compared with controls. The hypothermic response to ipsapirone was totally abolished in the depressed patients. When tested after a course of ECT, the seven depressed patients again showed reduced or blunted responses. We conclude that hypothalamic 5-HT(1A) receptor function is reduced in depression. In contrast to the effects of electroconvulsive shock (ECS) on post-synaptic 5-HT(1A) receptor function in animals, which have chiefly been measured in the hippocampus using electrophysiological techniques, ECT in humans does not induce an increase in sensitivity of post-synaptic 5-HT(1A) receptors in the hypothalamus.