Serotonin mediates the panicolytic-like effect of oxytocin in the dorsal periaqueductal gray

Autor(es)

De Oliveira Sergio, Thatiane ^[1] ; Frias, Alana Tercino ^[1] ; Vilela-Costa, Heloisa Helena ^[1] ; De Oliveira, Danielle C. G. ^[2] ; Zuardi, Antonio W. ^[2] ; Zangrossi Jr, Helio

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Div Psychiat, Sch Med Ribeirao Preto, Dept Neurosci & Behav, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PSYCHOPHARMACOLOGY; v. 34, n. 4 FEB 2020.
• Citações Web of Science: 0

Resumo

Introduction and objectives: Oxytocin (OT) has been widely linked to positive social interactions, and there is great interest in OT as a therapy for a variety of neuropsychiatric conditions. Recent evidence also suggests that OT can play an important role in the mediation of anxiety-associated defensive responses, including a role for serotonin (5-HT) neurotransmission in this action. However, it is presently unknown whether OT additionally regulates the expression of panic-related behaviors, such as escape, by acting in the dorsal periaqueductal gray (dPAG), a key panic-regulating area. This study aimed to investigate the consequence of OT injection in the dPAG on escape expression and whether facilitation of 5-HT neurotransmission in this midbrain area is implicated in this action. Methods: Male Wistar rats were injected with OT in the dPAG and tested for escape expression in the elevated T-maze (ETM) and dPAG electrical stimulation tests. Using the latter test, OT's effect was also investigated after previous intra-dPAG injection of the OT receptor antagonist atosiban, the preferential antagonists of 5-HT1A and 5-HT2A receptors, WAY-100635 and ketanserin, respectively, or systemic pretreatment with the 5-HT synthesis inhibitor p-CPA. Results: OT impaired escape expression in the two tests used, suggesting a panicolytic-like effect. In the ETM, the peptide also facilitated inhibitory avoidance acquisition, indicating an anxiogenic effect. Previous administration of atosiban, WAY-100635, ketanserin, or p-CPA counteracted OT's anti-escape effect. Conclusions: OT and 5-HT in the dPAG interact in the regulation of panic- and anxiety-related defensive responses. These findings open new perspectives for the development of novel therapeutic strategies for the treatment of anxiety disorders. (AU)

• Processo FAPESP: 17/18437-7 - Investigação do papel dos receptores 5-HT1A localizados nas asas laterais do núcleo dorsal da rafe no efeito panicolítico promovido pelo tratamento com fluoxetina
• Beneficiário: Heloísa Helena Vilela Costa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado