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

Mora, Miguel Pérez de la; Pérez-Carrera, Diana; Crespo-Ramírez, Minerva; Tarakanov, Alexander O.; Fuxé, Kjell; Borroto-Escuela, Dasiel O.

doi:10.1016/j.bbadis.2016.07.004

Cited by 47 publications

(62 citation statements)

References 61 publications

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“…Similarly, ICV oxytocin blocks dopamine release induced by ethanol administration within the NAc (Peters et al, 2017), which corresponds with reduced ethanol seeking behavior. Recent studies have characterized the presence of oxytocin/dopamine receptor complexes (OXTR-D2R) within the NAc in which oxytocin acts as an allosteric agonist to increase D2R affinity (de la Mora et al, 2016; Fuxe et al, 2012; Romero-Fernandez, Borroto-Escuela, Agnati, & Fuxe, 2013). Interestingly, activation of D2R reduces drug-seeking behavior and this receptor subtype is down-regulated following chronic drug exposure (for review see Koob & Mason, 2016; Volkow & Morales, 2015).…”

Section: Oxytocin As a Treatment For Addictionmentioning

confidence: 99%

Oxytocin and Rodent Models of Addiction

Leong

Cox

King

et al. 2018

International Review of Neurobiology

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Interest for the use of oxytocin as a treatment for addiction began over 40years ago. Better known for its roles in parturition, lactation and pair bonding, oxytocin also has anxiolytic properties, reduces immune and inflammatory responses, and has a role in learning and memory. In this chapter, oxytocin effects on addiction processes are described by highlighting research findings that have used oxytocin within current preclinical animal models of addiction, relapse, or craving. First, we provide a brief background of the endogenous oxytocin system followed by descriptions of the behavioral models used to study addiction, including models of drug taking and seeking. Then we review recent preclinical studies that have used oxytocin as a therapeutic intervention throughout multiple stages of the addiction cycle from a behavioral and neurobiological perspective. These models encompass the entire range of the addiction cycle including acquisition and maintenance of drug taking, withdrawal and craving during periods of drug abstinence, and ultimately relapse. We then posit several theories about how oxytocin interacts with both drug and social reward, as well as presenting a mechanistic account of how specific oxytocin receptor localization may contribute to oxytocin's efficacy as an addiction therapeutic.

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Section: Oxytocin As a Treatment For Addictionmentioning

confidence: 99%

Oxytocin and Rodent Models of Addiction

Leong

Cox

King

et al. 2018

International Review of Neurobiology

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“…In addition to acting as an acute anxiolytic to diminish fear responses, mainly in the CeA and other areas (Litvin et al 2016;Viviani et al 2011;de la Mora et al 2016;Sabihi et al 2017;Grund et al 2017;Menon et al 2018), OTcould also act on fear learning, and fear extinction learning in a longlasting manner. In other words, it could work on neuronal plasticity in the fear-related neural networks.…”

Section: Oxytocin Treatment: Mode Of Actionmentioning

confidence: 99%

Acute and long-lasting effects of oxytocin in cortico-limbic circuits: consequences for fear recall and extinction

Río¹,

Burg²,

Stoop³

et al. 2018

Psychopharmacology

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The extinction of conditioned fear responses entrains the formation of safe new memories to decrease those behavioral responses. The knowledge in neuronal mechanisms of extinction is fundamental in the treatment of anxiety and fear disorders. Interestingly, the use of pharmacological compounds that reduce anxiety and fear has been shown as a potent co-adjuvant in extinction therapy. However, the efficiency and mechanisms by which pharmacological compounds promote extinction of fear memories remains still largely unknown and would benefit from a validation based on functional neuronal circuits, and the neurotransmitters that modulate them. From this perspective, oxytocin receptor signaling, which has been shown in cortical and limbic areas to modulate numerous functions (Eliava et al. Neuron 89(6):1291-1304, 2016), among them fear and anxiety circuits, and to enhance the salience of social stimuli (Stoop Neuron 76(1):142-59, 2012), may offer an interesting perspective. Experiments in animals and humans suggest that oxytocin could be a promising pharmacological agent at adjusting memory consolidation to boost fear extinction. Additionally, it is possible that long-term changes in endogenous oxytocin signaling can also play a role in reducing expression of fear at different brain targets. In this review, we summarize the effects reported for oxytocin in corticolimbic circuits and on fear behavior that are of relevance for the modulation and potential extinction of fear memories.

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“…OTRs also form heterodimers with other Class A GPCRs. One compelling example includes the formation of heterodimers between OTRs and Dopamine (DA) 2 receptors (D2Rs), which, in turn, exhibit reciprocal interactions (Romero-Fernandez et al 2013; de la Mora et al 2016). Specifically OT activation increases D2R affinity for DA and DA agonists, while DA activation of D2Rs enhances OT-induced signaling.…”

Section: Summary Of Ot Ligands and Otr Pharmacologymentioning

confidence: 99%

“…Specifically, OT activation increases D2R affinity for DA and DA agonists, while DA activation of D2Rs enhances OT-induced signaling. With recently converging evidence for direct synergistic effects of OT neuronal release modulating DA neural activity and social behavior (Hung et al 2017;Xiao et al 2017), OTR/D2R heterodimers may represent an important physiological mechanism through which these behavioral outcomes can be modulated (De La Mora et al 2016). Whether OT ligand variants enhance or inhibit the conformational changes necessary to facilitate or impair OTR homodimerization and heterodimerization is an important area for future investigation.…”

Section: And Oxytocin Receptor Pharmacologymentioning

confidence: 99%

Oxytocin structure and function in New World monkeys: from pharmacology to behavior

Mustoe

Taylor

French

2018

Integrative Zoology

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Oxytocin (OT) is a hypothalamic nonapeptide that mediates a host of physiological and behavioral processes including reproductive physiology and social attachments. While the OT sequence structure is highly conserved among mammals, New World monkeys (NWMs) represent an unusual "hot spot" in OT structure variability among mammals. At least 6 distinct OT ligand variants among NWMs exist, yet it is currently unclear whether these evolved structural changes result in meaningful functional consequences. NWMs offer a new area to explore how these modifications to OT and its canonical G-protein coupled OT receptor (OTR) may mediate specific cellular, physiological and behavioral outcomes. In this review, we highlight relationships between OT ligand and OTR structural variability, specifically examining coevolution between OT ligands, OTRs, and physiological and behavioral phenotypes across NWMs. We consider whether these evolved modifications to the OT structure alter pharmacological profiles at human and marmoset OTRs, including changes to receptor binding, intracellular signaling and receptor internalization. Finally, we evaluate whether exogenous manipulation using OT variants in marmoset monkeys differentially enhance or impair behavioral processes involved in social relationships between pairmates, opposite-sex strangers, and parents and their offspring. Overall, it appears that changes to OT ligands in NWMs result in important changes ranging from cellular signaling to broad measures of social behavior.

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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

Cited by 47 publications

References 61 publications

Oxytocin and Rodent Models of Addiction

Oxytocin and Rodent Models of Addiction

Acute and long-lasting effects of oxytocin in cortico-limbic circuits: consequences for fear recall and extinction

Oxytocin structure and function in New World monkeys: from pharmacology to behavior

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