Spatial quantification of single cell mRNA and ligand binding of the kappa opioid receptor in the rat hypothalamus

Krogsbaek, Maiken; Larsen, Nick Yin; Landau, Anne M; Sanchéz, Connie; Nyengaard, Jens Randel

doi:10.1016/j.jchemneu.2022.102205

Cited by 4 publications

(3 citation statements)

References 29 publications

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“…We have previously shown a strong correlation between Oprk1 expression and KOR availability in control animals (39), and the same tendency is observed here. Signi cant increased Oprk1 expression is shown in the PVN following chronic OLZ treatment, and the same increase is observed in KOR levels in the PVN, however nonsigni cant.…”

Section: Discussionsupporting

confidence: 91%

“…Both the experiment and the image analysis procedure is described in length in Krogsbaek et al 2022 (39). In short, series of 20 µm sections were chosen for multiplex uorescence RNAscope in situ hybridization targeting Oprk1 (Probe-Rn-Oprk1, C1 channel, cat.…”

Section: Rnascope In Situ Hybridization and Image Analysismentioning

confidence: 99%

“…Receptor autoradiography targeting MOR, KOR and DOR was performed on fresh frozen 20 µm brain sections as previously described in detail in Krogsbaek (2022), where detailed image analysis is also described (39). For MOR detection, 4nM of [ 3 H]-DAMGO (NET902, Perkin Elmer) in 50 mM Tris-HCl (pH 7.4) assay buffer was used.…”

Section: In Vitro Receptor Autoradiography and Image Analysismentioning

confidence: 99%

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Chronic olanzapine treatment leads to increased opioid receptor expression and changes in feeding regulating neurons in the rat hypothalamus

Krogsbaek

Larsen

Yarmahmoudi³

et al. 2023

Preprint

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Opioid receptor antagonists have in recent years shown increasing promise as adjunct therapy to psychotropic medication. The goal is to reduce the weight gain and metabolic adverse effects that are associated with certain second generation antipsychotics, such as olanzapine (OLZ) and clozapine. In this study, female rats were treated for 4 weeks with a long-acting injectable formulation of OLZ at a dose that produced clinically relevant plasma levels to access effects on feeding regulation regions of the hypothalamus. Using quantitative spatial in situ hybridization and receptor autoradiography, expression levels of the mu, kappa and delta opioid receptors were defined in the five hypothalamic areas: paraventricular nucleus (PVN), arcuate nucleus (ARC), ventromedial nucleus (VMN), dorsomedial nucleus (DMN) and lateral hypothalamus (LH). In addition, hypothalamic neuron number and size were estimated using the optical fractionator and spatial rotator. Hyperphagia was observed after only 24 hours of OLZ treatment, with continued weight gain throughout the duration of the study. In contrast, the observed food intake reversed to control levels after 2 weeks of OLZ treatment. Blood samples from day 28 revealed no changes in metabolic markers compared to controls. Chronic OLZ treatment led to increased expression of kappa opioid receptor mRNA and receptor availability in the PVN, as well as increased mu opioid receptor availability in the PVN, ARC and VMN. These changes were accompanied by a decreased number of anorexigenic POMC neurons of the ARC and CRH neurons of the PVN. In conclusion, this study supports a connection between OLZ driven adverse metabolic effects and increased opioid receptor expression in the hypothalamus, thus providing a rationale for the positive effects of using opioid receptor antagonist to relieve OLZ adverse effects.

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Section: Discussionsupporting

confidence: 91%

Section: Rnascope In Situ Hybridization and Image Analysismentioning

confidence: 99%