Effects of ECS on 5-HT-1A Receptor Sensitivity in Hypothalamus: In Vivo Studies.

LERER, BERNARD; SHAPIRA, BARUCH; GUR, EITAN; GELFIN, YEVGENIA; NEWMAN, MICHAEL E.
Biological Psychiatry Laboratory, Hadassah - Hebrew University Medical Center, Ein Karem,, Jerusalem 91120, Israel.

Increased serotonergic transmission mediated by an increase in the sensitivity of post-synaptic 5-HT-1A receptors in the hippocampus has been proposed as a mechanism of action for electroconvulsive shock (ECS) in animals, and by inference for electroconvulsive therapy (ECT) in humans. However, there is little evidence for such a mechanism in other brain areas in experimental animals, or at all in human subjects. We have used in vivo microdialysis to measure 5-HT levels and 5-HT-1A receptor function in the rat hypothalamus, and neuroendocrine challenge tests to determine the effects of administration of a 5-HT-1A receptor agonist on activity of the hypothalamic-pituitary-adrenal axis in depressed patients and control subjects.
Basal 5-HT levels in rat hypothalamus were unaffected by a series of 10 ECS treatments given daily, with measurements performed 24 hr after the last treatment. However, presynaptic 5-HT-1A receptor sensitivity, as measured by the effect of a challenge dose of the 5-HT-1A agonist 8-OH-DPAT (0.2 mg/kg s.c.) to reduce 5-HT levels, was decreased after chronic ECS. Since activation of these receptors reduces firing of serotonergic neurons and 5-HT release, reduction in their sensitivity would be associated with increased 5-HT release and, hence, an increase in serotonergic transmission in the hypothalamus.
In 10 medication-free depressed patients, the cortisol response to challenge with the 5-HT-1A agonist, ipsapirone (0.3 mg/kg p.o.), was significantly reduced compared to that in 15 control subjects. The GH response to the agonist was slightly blunted in the depressed patients, while the hypothermic response to the agonist was completely abolished. 7 of the patients were re-tested after a course of ECT. The responses after treatment remained reduced or blunted. We conclude that in contrast to the effects of ECS on 5-HT-1A receptor in the hippocampus in animals, ECT in humans does not induce an increase in sensitivity of post-synaptic 5-HT-1A receptors in the hypothalamus. Whether presynaptic 5-HT-1A receptors are affected in humans remains to be established.