Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

Abstract

Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences Abstract Purpose: Antidepressant effects of analgesics have been investigate in both clinical and experimental studies. The purpose of this study was to investigate if the analgesic-antipyretic drug, dipyrone, also had antidepressant-like effects.Methods: Depression-like effects were investigated in an unpredictable chronic mild stress (UCMS) model in both male and female mice. Cage changes, light-dark cycle reversal, cage tilting, wet floor, empty cage, foreign material on the floor and predator sounds were used to induce light stress at different times for six weeks. Dipyrone was administered intraperitoneally beginning from the third week. Splash, rota-rod (RR) and forced swimming (FST) tests were performed at the seventh week as behavioural tests to evaluate the antidepressant-like effects of dipyrone. Coat state score (CSS) and weights of animals were recorded at seventh weeks. Results were analyzed using one or two-way ANOVA followed by the Bonferonni post hoc test.Results: Weight of UCMS-exposed mice did not change compared with controls; however, significant changes were observed in CSS in both sexes of stressed mice (p<0.05). RR latency decreased and immobility time enhanced in FST test in both sexes of stressed mice (p<0.05). Grooming behaviour was not different between the groups in female mice, but different in male mice in the splash test. Dipyrone did not produce a significant change in CSS in the UCMS-exposed group but reversed the latency time and immobility time to normal values in both sexes of mice and augmented the number of grooming behaviour only in stressed male mice. Conclusion:These results indicate that dipyrone produce antidepressant-like effects to some symptoms of UCMS according to gender.SUPPLEMENT

Antidepressant-like effects of Dipyrone researched with forced swim test

“…Daha önce yaptığımız çalışmada, farelerde öngörüle-meyen kronik stress modeli oluşturarak uyguladığı-mız dipironun çeşitli davranış testlerinde antidepresif benzeri etkisi olduğunu göstermiştik 34 . Bu çalışmada ise, zorunlu yüzdürme testiyle oluşturulan depresyon modelinde dipironun akut antidepresan-benzeri etkisinin olduğunu gösterdik.…”

Dipiron farelerde anksiyolitik-benzeri etkiler oluşturuyor mu?

“…Parasetamol (asetaminofen) ve dipiron (metamizol) diğer non-steroid anti-inflamatuvar ilaçlardan (NSAİİ) farklı olarak neredeyse hiç anti-inflamatuvar etkinlik göstermeyen, ancak analjezik ve antipiretik olarak günümüzde tüm dünyada sıklıkla kullanılan ilaçlardır. Çok eski ilaçlar olmalarına karşın halen etki mekanizmaları kesin olarak açıklığa kavuşmamıştır; uzun yıllardır analjezik etkilerinin santral komponentinin olduğu bildirilmesinin yanı sıra 7,8,9,10,11 son senelerde her iki ilacın da bazı etkilerine endojen kannabinoid sistemin aracılık ettiği bildirilmektedir. Öncelikle, parasetamol'ün analjezik etkilerine CB1 reseptörlerinin aracılık ettiği gösterilmiş 12,13 daha sonra parasetamol'ün araşidonil amid metaboliti olan AM-404'ün, endokannabinoidleri degrade eden yağ asidi amid hidrolaz (FAAH) enzimini ve endokannabinoidlerin geri-alımını inhibe ederek endokannabinoid düzeylerini arttırdığı belirlenmiştir 14 .…”