Effects of chronic antidepressants and electroconvulsive shock on serotonergic neurotransmission in the rat hypothalamus: microdialysis studies in vivo

Effects of chronic antidepressants and electroconvulsive shock on serotonergic neurotransmission in the rat hypothalamus: microdialysis studies in vivo.

Eliyahu Dremencov, Eitan Gur, Michael E. Newman and Bernard Lerer
Biological Psychiatry Lab., Dept. of Psychiatry, Hadassah - Hebrew University Medical Center, P.O.B. 12000 Jerusalem 91120 Israel.

The aim of this work was to examine the effects of chronic treatment with the tricyclic antidepressant, clomipramine, and electroconvulsive shock (ECS) on serotonergic neurotransmission in the hypothalamus. In neuroendocrine challenge paradigms, it was found that serotonin 5-HT1A receptor agonists activated ACTH and cortisol/corticosterone release, and this activation was reduced in depressed patients. Serotonergic neurotransmission in the hypothalamus is negatively regulated by somatodendritic 5-HT1A autoreceptors and nerve terminal 5-HT1B autoreceptors. We determined the effects of chronic administration of clomipramine and ECS on 5-HT1A and 5-HT1B autoreceptor mediated control of serotonin release in the hypothalamus. Methods. Clomipramine was given by miniosmotic pumps at dosage of 10 mg/kg/day for 28 days. ECS was given via ear clip electrodes daily for 10 days. Microdialysis probes were implanted into the hypothalamus and perfused with Ringer's solution at 0.5 ml/min. 5-HT levels were determined by HPLC.
Results. Chronic treatment with clomipramine decreased the 5-HT response to the systemic administration of 5 mg/kg of the selective 5-HT1B autoreceptor antagonist, GR 127935, but did not affect the 5-HT response to the systemic administration of 0.2 mg/kg of the selective 5-HT1A receptor agonist 8-OH-DPAT. Chronic ECS administration decreased the 5-HT response to the 8-OH-DPAT but did not affect the 5-HT response to the GR 127935 .
Conclusion. Clomipramine administration decreased 5-HT1B autoreceptor activity and ECS decreased 5-HT1A autoreceptor activity. Thus, serotonergic neurotransmission in the hypothalamus was increased after chronic treatment both with clomipramine and with ECS.