Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats

Jérôme Mairesse, Eleonora Gatta, Marie Line Reynaert, Jordan Marrocco, Sara Morley-Fletcher, Marion Soichot, Lucie Deruyter, Gilles Van Camp, Hammou Bouwalerh, Francesca Fagioli, Anna Pittaluga, Delphine Allorge, Ferdinando Nicoletti, Stefania Maccari

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1. mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life.

Original languageEnglish
Pages (from-to)36-46
Number of pages11
JournalPsychoneuroendocrinology
Volume62
DOIs
Publication statusPublished - Dec 1 2015

Fingerprint

Oxytocin Receptors
Presynaptic Receptors
Glutamic Acid
Hippocampus
Amygdala
Hypothalamus
Social Behavior
Synaptic Transmission
gamma-Aminobutyric Acid
Glucocorticoids
Genes
Psychiatry
Anxiety
Phenotype
Pregnancy
carbetocin

Keywords

  • Anxiety
  • Carbetocin
  • Glutamate
  • Perinatal stress
  • Social behavior
  • Ventral hippocampus

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Endocrine and Autonomic Systems

Cite this

Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats. / Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania.

In: Psychoneuroendocrinology, Vol. 62, 01.12.2015, p. 36-46.

Research output: Contribution to journalArticle

Mairesse, J, Gatta, E, Reynaert, ML, Marrocco, J, Morley-Fletcher, S, Soichot, M, Deruyter, L, Camp, GV, Bouwalerh, H, Fagioli, F, Pittaluga, A, Allorge, D, Nicoletti, F & Maccari, S 2015, 'Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats', Psychoneuroendocrinology, vol. 62, pp. 36-46. https://doi.org/10.1016/j.psyneuen.2015.07.005
Mairesse, Jérôme ; Gatta, Eleonora ; Reynaert, Marie Line ; Marrocco, Jordan ; Morley-Fletcher, Sara ; Soichot, Marion ; Deruyter, Lucie ; Camp, Gilles Van ; Bouwalerh, Hammou ; Fagioli, Francesca ; Pittaluga, Anna ; Allorge, Delphine ; Nicoletti, Ferdinando ; Maccari, Stefania. / Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats. In: Psychoneuroendocrinology. 2015 ; Vol. 62. pp. 36-46.
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