• Husbands, Stephen
• Liu, Nairong
• Bailey, Sarah

Abstract

Introduction: Self-grooming is an innate behaviour of rodents. A decrease in self-grooming has been reported to be negatively correlated with depressive behaviour in the forced swim test in rats (Shiota et al. 2016, J Physiol. Sci. 66: 265) and has been suggested to reflect deficits in self-care in human psychiatric illness (Butelman et al. 2021, J Psychopharmacol. 35: 579). Furthermore, the area of the brain associated with self-grooming are also implicated in the regulation of mood. Here, we have investigated the potential utility of the splash test as a screen for antidepressant efficacy.<br/><br/>Methods: Adult male and female C57BL/6 mice (7-8 weeks, University of Bath) were handled twice before the test. Mice were habituated to the procedure by spraying ~0.6ml of tap water onto the dorsal surface. On test day, animals were injected with saline or U50,488 (3.2mg/kg; 5mg/kg), ketamine (10 mg/kg), naltrexone (1mg/kg) and desipramine (10 mg/kg) intraperitoneally 30min before testing (N=30; n=10 saline/desipramine group; n=5 ketamine/naltrexone group). For the test, mice were placed in a clean novel test cage individually with a transparent lid. After 1min exploration, the lid was removed and ~0.6 ml of 10% sucrose solution was sprayed on the dorsal surface of the mouse. Behaviour was recorded for 5 min and the time spent grooming determined. Data were analysed using a 2-way ANOVA, with Sex and Treatment as factors, followed by planned comparisons (LSD test) of the predicted means (InVivo Stat v4.7).<br/><br/>Results: There was a significant effect of treatment [F(3,61)= 17.14, P&lt;0.0001] but no effect of sex [F(1,61)=3.14, P=0.08] nor interaction between the factors [F(3,61)=0.1, P=0.9]. In both males and females, U50,488 significantly decreased the time spent grooming in the splash test (Ps&lt;0.01). Desipramine and naltrexone had no significant effect on grooming time. Ketamine, significantly increased the grooming time only in male mice (P=0.02).<br/><br/>Conclusion: Grooming behaviour in a 10% sucrose splash test in C57BL/6 mice was sensitive to the kappa opioid receptor (KOP) agonist U50,488. As others have shown (Butelman et al. 2019), activation of KOP is associated with a stress-induced decrease in grooming. However, the test is not sensitive to the non-selective KOP antagonist naltrexone and the tricyclic antidepressantdesipramine. These data suggest that in C57BL/6 mice, the splash test in this assay, does not have widespread utility as a screen for antidepressant efficacy across multiple drug classes.<br/>

Topics

• impedance spectroscopy
• surface
• activation