Evidence for the existence of facilitatory interactions between the dopamine D2 receptor and the oxytocin receptor in the amygdala of the rat. Relevance for anxiolytic actions

Abstract

Introduction: The amygdala is a limbic region of high value for understanding anxiety and its treatment. Dopamine D2 receptors (D2Rs) and oxytocin receptors (OXTRs) have both been shown to participate in modulating anxiety involving effects in the amygdala. The goal is to understand if D2R–OXTR heterocomplexes exist in the central amygdala and if, through enhancing allosteric receptor–receptor interactions, may enhance anxiolytic actions.Methods: The methods used involve the shock-probe burying test, the in situ proximity ligation assay (PLA), image acquisition and analysis, and the BRET2 assay. Bilateral cannulas were introduced into the amygdala, and the effects of the coadministration of oxytocin and the D2R-like agonist quinpirole into the amygdala were studied.Results: The combination treatment enhanced the anxiolytic effects compared to the single treatment. The D2R/D3R antagonist raclopride blocked the effects of the combination treatment of oxytocin and the D2R agonist, although oxytocin is regarded as a distinct modulator of fear-mediating anxiolytic effects. In situ PLA results indicate the existence of D2R–OXTR heteroreceptor complexes and/or the co-location of OXTR and D2R within the same cell membrane nanodomains in the central amygdala. With BRET2, evidence is given for the existence of D2R–OXTR heteromers in HEK293 cells upon co-transfection.Discussion: The enhanced behavioral effects observed upon co-treatment with OXTR and D2R agonists may reflect the existence of improved positive receptor–receptor interactions in the putative D2R–OXTR heterocomplexes in certain neuronal populations of the basolateral and central amygdala. The D2R–OXTR heterocomplex, especially upon agonist co-activation in the central amygdala, may open a new pharmacological venue for the treatment of anxiety.

Neuropeptide Y receptor 1 and galanin receptor 2 (NPY1R-GALR2) interactions in the dentate gyrus and their relevance for neurogenesis and cognition

“…To understand the cellular effects following coadministration of NPY1R and GALR2 agonists we studied the presence of putative NPY1R-GALR2 heteroreceptor complexes on dorsal DG. As in situ PLA typically provides a resolution in the range of 25−30 nm when secondary IgG antibodies are used, we cannot exclude the possibility that in our current experiments, we may detect NPY1R-GALR2 heteroreceptor complexes and/or the co-location of NPY1R and GALR2 within the same cell membrane nanodomains (hereafter referred to as heterocomplexes) ( Hernández-Mondragón et al, 2023 ). This technique permits accurate location of putative NPY1R-GALR2 heteroreceptor complexes.…”

The psychophysiology of music-based interventions and the experience of pain

“…These are dynamically regulated (Cahill et al, 2007) cell surface receptors that are coupled to so-called G proteins that regulate diverse cellular functions. Different GPCRs can come together to form complexes that influence their functionality, resulting in altered down-stream intracellular signaling (Borroto-Escuela et al, 2017Chruścicka et al, 2019;Hernández-Mondragón et al, 2023). From a music and pain perspective, potentially relevant GPCR complexes include dopamine and serotonin receptors, oxytocin and serotonin receptors, oxytocin and dopamine receptors, and dopamine and glutamate receptors.…”