RT Journal Article
T1 Signaling in dopamine D2 receptor-oxytocin receptor heterocomplexes and its relevance for the anxiolytic effects of dopamine and oxytocin interactions in the amygdala of the rat
A1 de la Mora, Miguel Pérez
A1 Pérez-Carrera, Diana
A1 Crespo-Ramírez, Minerva
A1 Tarakanov, Alexander
A1 Fuxe, Kjell
A1 Borroto-Escuela, Dasiel O.
K1 Dopamina - Receptores
K1 Receptores
AB Dopamine D2 receptor (D2R)–oxytocin receptor (OTR) interactions exist within heterocomplexes with facilitatory effects on D2R recognition and Gi/o coupling. In this work the hypothesis is tested using cotransfected HEK293 cells whether allosteric reciprocal D2R-OTR interactions can enhance signaling of D2R-OTR heterocomplexes along the CREB, MAPK and PLC pathways and whether the anxiolytic effects of OT may involve facilitatory D2R-OTR interactions within the central amygdaloid nucleus (CeA). Oxytocin enhanced the D2-like agonist quinpirole induced inhibition of the AC-PKA-pCREB signaling cascade and increased its signaling over the RAS-MAPK-pELK pathway. Quinpirole enhanced the oxytocin induced increases in the activity of the PLCbeta-IP3-calcineurin and RAS-MAPK-pELK cascades. Bilateral infusion of oxytocin (0.9–150 ng/side) into the CeA of the rat elicited anxiolytic effects in the Shock-Probe Burying test, an unconditioned model of fear/anxiety. This action was not observed when oxytocin (25 ng/side) was simultaneously co-infused with raclopride (neither 250 nor 500 ng/side), a D2/D3 antagonist, into the CeA. Based on the current findings, the blockade of the anxiolytic effects of oxytocin by the simultaneous intra-CeA administration of raclopride can be explained by a lack of facilitatory protomer interactions in D2R-OTR heterocomplexes. Dysfunction and/or disruption of such interactions in the central amygdala may lead to anxiety development. Restoration of such interactions may represent a new strategy for development of novel anxiolytic drugs.
PB Elsevier
SN 09254439
YR 2016
FD 2016-11-01
LK https://hdl.handle.net/10630/45013
UL https://hdl.handle.net/10630/45013
LA eng
NO Miguel Pérez de la Mora, Diana Pérez-Carrera, Minerva Crespo-Ramírez, Alexander Tarakanov, Kjell Fuxe, Dasiel O. Borroto-Escuela, Signaling in dopamine D2 receptor-oxytocin receptor heterocomplexes and its relevance for the anxiolytic effects of dopamine and oxytocin interactions in the amygdala of the rat, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1862, Issue 11, 2016, Pages 2075-2085, ISSN 0925-4439, https://doi.org/10.1016/j.bbadis.2016.07.004. (https://www.sciencedirect.com/science/article/pii/S0925443916301648)
NO Swedish Research Council (Vetenskapsrådet)
NO Dirección General de Asuntos del Personal Académico (DGAPA), UNAM (México)
NO CONACYT (Consejo Nacional de Ciencia y Tecnología, México)
NO AFA Försäkring (Suecia)
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 13 abr 2026