Hypothalamic paraventricular, but not supraoptic neurons, mediate the serotonergic stimulation of oxytocin secretion.
The purpose of the present studies was to determine whether cells in the hypothalamic paraventricular (PVN) or supraoptic (SON) nuclei mediate the serotonergic stimulation of oxytocin secretion. The serotonergic stimulus consisted of injection of the 5-HT-releasing drug p-chloroamphetamine (8 mg/kg, IP). The validity of this approach was verified by comparing this drug with another 5-HT releaser, d-fenfluramine (5 mg/kg, IP). Both 5-HT releasers increased plasma oxytocin concentration. Furthermore, the 5-HT uptake blocker fluoxetine (10 mg/kg, IP) blocked the effects of both p-chloroamphetamine and d-fenfluramine on plasma oxytocin concentrations, suggesting that both 5-HT releasers must be taken up through the 5-HT transporter into 5-HT nerve terminals to increase oxytocin secretion. In the lesion experiments, cells in the hypothalamic PVN or SON were destroyed by injection of the cell-selective neurotoxin ibotenic acid. The PVN lesions reduced basal levels and inhibited the effect of p-chloroamphetamine (8 mg/kg, IP) on plasma oxytocin concentration. In contrast, SON lesions did not alter basal oxytocin levels and did not reduce the oxytocin response to p-chloroamphetamine, suggesting that the SON is not involved in the serotonergic stimulation of oxytocin secretion. Site specificity of the PVN lesions was confirmed when injections of ibotenic acid into the hypothalamic dorsomedial nucleus (DMN), immediately caudal to the PVN, potentiated the oxytocin response to p-chloroamphetamine, suggesting that the DMN exerts an inhibitory influence on the secretion of oxytocin. Taken together, the data suggest that the serotonergic stimulation of oxytocin secretion involves PVN, but not SON, oxytocin neurons.
Van de Kar
L D
LD
Loyola University Chicago, Department of Pharmacology, Maywood, IL 60153.
Rittenhouse
P A
PA
Li
Q
Q
Levy
A D
AD
Brownfield
M S
MS
D000818:Animals; D005277:Fenfluramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D007051:Ibotenic Acid / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010121:Oxytocin / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000502:physiology*; D010133:p-Chloroamphetamine / Q000494:pharmacology
D005473:Fluoxetine; D007051:Ibotenic Acid; D005277:Fenfluramine; D012701:Serotonin; D010121:Oxytocin; D010133:p-Chloroamphetamine