Received for publication December 10, 2004.
Revised February 22, 2005.
Accepted for publication February 23, 2005.

5-HT1A receptors in the paraventricular nucleus of the hypothalamus mediate oxytocin and adrenocorticotropin hormone release as well as some behavioral components of the serotonin syndrome

Abstract

Neuroendocrine responses to administration of serotonin releasing agents or 5-HT1A-receptor agonists have been used as an index of serotonin receptor function in patients with depression and other mood disorders. However, the location and receptor population that mediates these responses have not been clearly identified. We tested the hypothesis that 5-HT1A receptors in the paraventricular nucleus of the hypothalamus (PVN) mediate the release of adrenocorticotropin hormone (ACTH) and oxytocin after administration of a selective 5-HT1A agonist in conscious rats. Low dose infusion (1 nmol/100 nl/side) of the selective 5-HT1A antagonist, WAY100635 (WAY), into the PVN blocked the rise in ACTH and oxytocin stimulated by low dose (30 nmol/kg), iv administration of the 5-HT1A agonist, 8-OH-DPAT (274 ± 53 vs. 70 ± 20 pg/ml, p<0.01 for ACTH and 10.7 ± 3.4 vs. 4.6 ± 0.7 pg/ml, p<0.05 for oxytocin after saline or WAY pre-treatment respectively). WAY did not influence the bradycardic effect of 8-OH-DPAT (-56 ± 7 vs. -54 ± 6 bpm after saline or WAY). 8-OH-DPAT treatment also elicited locomotor activation followed by hindlimb abduction and flat body posture. Surprisingly, WAY attenuated some aspects of locomotor activation and reduced the duration of hindlimb abduction elicited by the agonist (5.1 ± 0.9 vs. 0.3 ± 0.3 min for saline or WAY-treated rats). These data indicate that 5-HT1A-receptor stimulation in the PVN mediates the characteristic neuroendocrine response to serotonin agonist challenge. Moreover, they provide the first evidence that aspects of the behavioral serotonin syndrome are mediated by forebrain hypothalamic receptors.

Key words: 8-OH-DPAT, behavior, blood pressure, heart rate, paraventricular, serotonin

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