title: 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.
abstract: 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 (0.9-150ng/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 (25ng/side) was simultaneously co-infused with raclopride (neither 250 nor 500ng/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.
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico. Electronic address: mperez@ifc.unam.mx.
authors.forename: Miguel Pérez
authors.initials: MP
authors.lastname: de la Mora
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico. Electronic address: dianaperezcarrera@hotmail.com.
authors.forename: Diana
authors.initials: D
authors.lastname: Pérez-Carrera
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico. Electronic address: mcrespo@ifc.unam.mx.
authors.forename: Minerva
authors.initials: M
authors.lastname: Crespo-Ramírez
authors.affiliation: Russian Academy of Sciences, Saint Petersburg Institute for Informatics and Automation, Saint Petersburg, Russia. Electronic address: sasha_tar@hotmail.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tarakanov
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. Electronic address: kjell.fuxe@ki.se.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden; Department of Biomolecular Science, Section of Physiology, University of Urbino, Campus Scientifico Enrico Mattei, via Ca' le Suore 2, I-61029 Urbino, Italy. Electronic address: dasiel.borroto.escuela@ki.se.
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
keywords: Amygdala; Anxiety; Dopamine D2 receptor; Fear; Heteroreceptor complexes; Oxytocin; Oxytocin receptor; Raclopride; Receptor-receptor interactions