Profile of a short-acting κ-antagonist, LY2795050, on self-grooming behaviors, forced swim test and locomotor activity: sex comparison in mice
| Autor: | Mary Jeanne Kreek, Eduardo R. Butelman, Caroline Baynard, Bryan D. McElroy, Thomas E. Prisinzano |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Pyrrolidines Narcotic Antagonists Dynorphin Locomotor activity Self grooming 03 medical and health sciences Mice 0302 clinical medicine Sex Factors Internal medicine Medicine Animals Pharmacology (medical) Receptor Swimming 030304 developmental biology Pharmacology 0303 health sciences Behavior Animal Dose-Response Relationship Drug business.industry Receptors Opioid kappa Antagonist 3 4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide (trans)-Isomer Anhedonia Grooming Mice Inbred C57BL Psychiatry and Mental health Endocrinology Benzamides Female medicine.symptom business 030217 neurology & neurosurgery Kappa Locomotion Behavioural despair test |
| Zdroj: | Journal of psychopharmacology (Oxford, England). 35(5) |
| ISSN: | 1461-7285 |
| Popis: | Background: Novel short-acting κ(kappa)-opioid receptor selective antagonists are translational tools to examine the impact of the κ-receptor/dynorphin system in assays related to central nervous system dysfunction (e.g., substance use disorders, anhedonia and depression). The effects of such compounds have been compared in males and females under very limited conditions. Aims: The goal of this study was to examine potential sex differences in the effects of a κ-agonist and a short-acting κ-antagonist in an ethologically relevant test of anhedonia, the “splash test” of self-grooming, and also in the forced swim test and in locomotor activity. Methods: We examined the dose-dependence of grooming deficits caused by the κ-agonist U50,488 (0.1–3.2 mg/kg intraperitoneal (i.p.)) in gonadally intact adult male and female C57BL/6J mice. We then compared the effects of the short-acting κ-antagonist LY2795050 ((3-chloro-4-(4-(((2S)-2-pyridin-3-ylpyrrolidin-1-yl)methyl) phenoxy)benzamide)); 0.032–0.1 mg/kg i.p.) in blocking grooming deficits caused by U50,488 (3.2 mg/kg). The effects of LY2795050 were also studied in the forced swim test (FST). The effects of LY2795050 in blocking the locomotor depressant effects of U50,488 (10 mg/kg) were also studied. Results: U50,488 produced dose-dependent grooming deficits in male and female mice, and LY2795050 prevented these effects. In contrast, LY2795050 decreased immobility in the FST in males at a dose of 0.1 mg/kg, but not in females, up to a dose of 0.32 mg/kg. Also, LY2795050 (0.32 mg/kg) prevented and also reversed the locomotor-depressant effects of U50,488 (10 mg/kg), in males and females. Conclusions: This study further implicates the κ-receptor system in ethologically relevant aspects of anhedonia, and confirms sexual dimorphism in some behavioral effects of novel κ-antagonists. |
| Databáze: | OpenAIRE |
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