Pitolisant protects mice chronically treated with corticosterone from some behavioral but not metabolic changes in corticosterone-induced depression model

被引:5
|
作者
Kotanska, Magdalena [1 ]
Mika, Kamil [1 ]
Salaciak, Kinga [2 ]
Wheeler, Lee [3 ]
Sapa, Jacek [1 ]
Kiec-Kononowicz, Katarzyna [4 ]
Pytka, Karolina [2 ]
机构
[1] Jagiellonian Univ, Dept Pharmacol Screening, Med Coll, 9 Med St, PL-30688 Krakow, Poland
[2] Jagiellonian Univ, Fac Pharm, Dept Pharmacodynam, Med Coll, Krakow, Poland
[3] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland
[4] Jagiellonian Univ, Fac Pharm, Dept Technol & Biotechnol Drugs, Med Coll, Krakow, Poland
关键词
Pitolisant; Corticosterone; Depressive-like behavior; Metabolic disturbance; Sigma-1; receptor; H-3 histamine receptor; SIGMA-RECEPTOR AGONISTS; ANTIDEPRESSANT; LIGANDS; H-3; REVERSES; BDNF; ANTAGONIST; EXPRESSION; DECREASE; ANXIETY;
D O I
10.1016/j.pbb.2020.172974
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Purpose: Histamine H-3 receptor ligands may have antidepressant and anxiolytic effects. They can also cornpensate for metabolic disorders, which affect glucose or triglyceride levels. In previous studies, we have shown that pitolisant, a histamine H-3 receptor antagonist/inverse agonist and al receptor agonist, prevented the development of certain metabolic and depressive-like disorders in mice that have been treated chronically with olanzapine. Methods: As a continuation of our previous experiments, this study aimed to investigate the antidepressant- and anxiolytic-like activity of pitolisant in mice using the corticosterone-induced depression model. The forced swim and the elevated plus maze tests were used as behavioral endpoints. We also studied the effect pitolisant had on the level of acetoacetic acid in the urine as well as the glucose tolerance and body weight of the mice that had been administered corticosterone. Results: Pitolisant (10 mg/kg b.w.) did not prevent depressive-like behavior in mice during the chronic corticosterone administration but did counteract anxiety-like behavior, whilst fluoxetine (10 mg/kg) was shown to protect the mice from both of these behaviors. None of the treatments that were used in the study showed an effect on the locomotor activity of the mice. Pitolisant did not prevent an increase in acetoacetic acid levels in the urine, nor did it improve glucose tolerance in the tested mice. Conclusion: Although literature data indicates that there is significant potential for finding an antidepressant and anti-diabetic drug among the histamine H-3 and sigma 1 receptor ligands, in our study, pitolisant was shown to only slightly compensate for corticosterone-induced abnormalities. However, further research will be required to study pitolisant's anxiolytic-like activity.
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页数:7
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