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Serotonin mediates the panicolytic-like effect of oxytocin in the dorsal periaqueductal gray.
J Psychopharmacol. 2020 04; 34(4):383-390.JP

Abstract

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

De Oliveira Sergio T
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Frias AT
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Vilela-Costa HH
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
De Oliveira DC
Department of Neurosciences and Behavior, Division of Psychiatry, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Zuardi AW
Department of Neurosciences and Behavior, Division of Psychiatry, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Zangrossi H
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.

MeSH

AnimalsAnti-Anxiety AgentsBehavior, AnimalElectric StimulationElectrodes, ImplantedEscape ReactionMaleOxytocinPanicPeriaqueductal GrayRatsRats, WistarReceptor, Serotonin, 5-HT1AReceptor, Serotonin, 5-HT2AReceptors, OxytocinSerotoninSerotonin AntagonistsSynaptic TransmissionVasotocin

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32108540

Citation

De Oliveira Sergio, Thatiane, et al. "Serotonin Mediates the Panicolytic-like Effect of Oxytocin in the Dorsal Periaqueductal Gray." Journal of Psychopharmacology (Oxford, England), vol. 34, no. 4, 2020, pp. 383-390.
De Oliveira Sergio T, Frias AT, Vilela-Costa HH, et al. Serotonin mediates the panicolytic-like effect of oxytocin in the dorsal periaqueductal gray. J Psychopharmacol. 2020;34(4):383-390.
De Oliveira Sergio, T., Frias, A. T., Vilela-Costa, H. H., De Oliveira, D. C., Zuardi, A. W., & Zangrossi, H. (2020). Serotonin mediates the panicolytic-like effect of oxytocin in the dorsal periaqueductal gray. Journal of Psychopharmacology (Oxford, England), 34(4), 383-390. https://doi.org/10.1177/0269881120907960
De Oliveira Sergio T, et al. Serotonin Mediates the Panicolytic-like Effect of Oxytocin in the Dorsal Periaqueductal Gray. J Psychopharmacol. 2020;34(4):383-390. PubMed PMID: 32108540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serotonin mediates the panicolytic-like effect of oxytocin in the dorsal periaqueductal gray. AU - De Oliveira Sergio,Thatiane, AU - Frias,Alana Tercino, AU - Vilela-Costa,Heloisa Helena, AU - De Oliveira,Danielle Cg, AU - Zuardi,Antônio W, AU - Zangrossi,Hélio,Jr Y1 - 2020/02/28/ PY - 2020/2/29/pubmed PY - 2021/6/29/medline PY - 2020/2/29/entrez KW - Oxytocin KW - dPAG KW - panic KW - serotonin SP - 383 EP - 390 JF - Journal of psychopharmacology (Oxford, England) JO - J Psychopharmacol VL - 34 IS - 4 N2 - 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. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/32108540/Serotonin_mediates_the_panicolytic_like_effect_of_oxytocin_in_the_dorsal_periaqueductal_gray_ DB - PRIME DP - Unbound Medicine ER -