Agomelatin Yetişkin Sıçanlarda Skopolamin Kaynaklı Öğrenme ve Hafıza Bozukluğunu Tersine Çevirir

Öz

Amaç: Agomelatin, melatonin reseptör (MT1 ve MT2) agonisti ve serotonin reseptör (5-HT2C) antagonisti olan antidepresan bir ilaçtır. Artan kanıtlar, agomelatinin nöroprotektif ve nöromodülatör etkiye sahip olduğunu göstermektedir. Bu çalışmada skopolamin indüklü bilişsel yetmezlik oluşturulan sıçanlarda agomelatinin potansiyel etkileri araştırılmıştır.

Materyal ve Metot: Erişkin erkek sıçanlara 21 gün süreyle skopolamin (1 mg/kg) ve agomelatin (40 mg/kg) uygulandı. İlaç uygulamalarını takiben sıçanlar bilişsel davranışların değerlendirilebilmesi amacıyla yeni nesne tanıma (YNT) ve Morris su labirenti (MSL) testine tabi tutuldu. İlave olarak, beyin nörokimyasal analizleri için hipokampus ve prefrontal kortekste beyin-türevi nörotrofik faktör (BDNF) ve asetilkolin (ACh) düzeyleri değerlendirildi.

Bulgular: Skopolamin hem uzamsal hafızayı hem de ayırt etme indeksini önemli ölçüde azalttı (p<0,05). Agomelatin tedavisi uzamsal hafıza performansını ve keşif süresini arttırdı, ancak ayrımcılık indeksini etkilemedi (P>0,05). Ayrıca agomelatin, skopolamin grubuna kıyasla hem hipokampusta hem de prefrontal kortekste BDNF düzeylerini önemli ölçüde arttırdı (sırasıyla p<0,05, p<0,01). Diğer yandan grupların ACh düzeyleri arasında istatistiksel olarak anlamlılık bulunmadı (p>0,05).

Sonuç: Birlikte ele alındığında, bu sonuçlar agomelatinin skopolamin kaynaklı hafıza yetmezliğinin hafifletilmesinde belirgin rol oynadığını göstermiştir. Bu nedenle, agomelatinin bilişsel yetmezliğin önlenmesinde potansiyel bir ajan olabileceğini öne sürüyoruz.  

Anahtar Kelimeler

• Agomelatin
• asetilkolin
• BDNF
• bellek
• bilişsel yetmezlik

Agomelatine Reverses Scopolamine-Induced Learning and Memory Impairment in Adult Rats

Abstract

Objective: The antidepressant agomelatine agent is a melatonin receptor (MT1 and MT2) agonist and a serotonin receptor (5-HT2C) antagonist. Increasing evidence shows that agomelatine has neuroprotective and neuromodulatory effects. In this study, the potential effects of agomelatine in rats with scopolamine-induced cognitive impairment were investigated.

Materials and Methods: Adult male rats were administered scopolamine (1 mg/kg) and agomelatine (40 mg/kg) for 21 days. After drug administration, rats were subjected to new object recognition (NOR) and Morris water maze (MWM) tests in order to evaluate cognitive behaviors. In addition, brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels in the hippocampus and prefrontal cortex were evaluated.

Results: Scopolamine significantly decreased both spatial memory and discrimination index (p<0.05). Agomelatine treatment increased spatial memory performance and exploration time, but did not affect the discrimination index (P>0.05). In addition, agomelatine significantly increased BDNF levels in both hippocampus and prefrontal cortex compared to the scopolamine group (p<0.05, p<0.01, respectively). On the other hand, there was no statistically significant difference between the ACh levels of the groups (p>0.05).

Conclusion: Taken together, these results demonstrated that agomelatine plays a important role in alleviating scopolamine-induced memory impairment. Therefore, we suggest that agomelatine may be a potential agent in the prevention of cognitive impairment.  

Keywords

• Cognitive impairment
• agomelatine
• spatial memory
• BDNF
• acetylcholine

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