The expression level of muscarinic M1 receptor subtypes in different regions of rat brain

Yıl 2017, , 162 - 168, 22.10.2017

Aslı Aykac , Buse Karanlık

https://doi.org/10.5472/marumj.370855

Öz

Objectives: Post-traumatic stress disorder (PTSD) is characterized

by life threatening trauma, overexcitation, flashbacks and

nightmares. Research on PTSD is faced with the challenge of

understanding how a traumatic experience leads to long lasting

detrimental effects on behavior and functions of the brain. Many

pharmacological agents are available in the pharmacotherapy

of the PTSD where there is no adequate evidence to support the

efficacy of any specific agent. It is hypothesized that M1 muscarinic

receptor subtypes might play important role in the recall of

negative experience. The aim of this research is to investigate both

the behavioral and the molecular efficacy of chronic fluoxetine

(FLU) (2.5mg/day; i.p) treatment in PTSD and also the probable

effect of pharmacotherapy on M1 muscarinic receptor subtype

expression in rats.

Materials and Methods: For experimental design random

selection was performed to all groups; Control, Stress and

Treatment groups. The effects of chronic FLU treatment were

evaluated in terms of expression levels of the M1 receptors in the

hippocampus and the frontal cortex of the rats’ brain.

Results: When the rats were subjected to the trauma reminder

on the last day of the experiment (Day 30), the anxiety indexes

of the stress group were found to be significantly higher than the

control (P< 0.001). Moreover, it has been observed that chronic

FLU treatment restored the anxiety scores in stress groups by

lowering the anxiety indexes (P< 0.001).

Conclusion: In this study, it has been indicated that stress

induces anxiety like behavior and reduces M1 expression in the

hippocampus and the frontal cortex of the rats’ brain. These effects

can be prevented by lowering the dose of chronic FLU therapy.

Anahtar Kelimeler

Muscarinic receptors, Stress, Cat litter, Fluoxetine, Hippocampus, Frontal cortex

Sıçan farklı beyin bölgelerinde M1 muskarinik reseptör alt tipi seviyeleri

Öz

Amaç: Travma sonrası stres bozukluğu (TSSB) yaşamı tehdit eden

travma, aşırı uyarılma, flashbackler ve kabuslar ile karakterizedir.

TSSB araştırmaları, travmatik bir deneyimin beyinin davranış

ve işlevleri üzerinde uzun süreli bozulma etkilerine yol açtığını

anlamanın zorluğuyla karşı karşıyadır. Herhangi bir spesifik ajanın

etkinliğini destekleyecek uygun kanıt olmadığında, TSSB’nin

farmakoterapisinde birçok farmakolojik ajan kullanılmaktadır.

Olumsuz bir deneyimin geri çağrılmasında M1 muskarinik reseptör

alt tiplerinin önemli rol oynayabileceği öngörülmektedir. Bu

araştırmanın amacı, TSSB’de kronik fluoksetin (FLU) (2.5 mg/

gün; i.p) tedavisinin hem davranışsal hem de moleküler etkinliğini

ve farmakoterapinin sıçanlarda M1 muskarinik reseptör alt tipi

ekspresyonu üzerine muhtemel etkisini araştırmaktır.

Gereç ve Yöntem: Deney tasarımında tüm gruplar rastgele

olarak seçilerek Kontrol, Stres ve Tedavi grupları oluşturulmuştur.

Kronik FLU tedavisinin etkileri, sıçan hipokampüs ve frontal

korteksinde, M1 reseptörlerinin ekspresyon seviyeleri açısından

değerlendirilmiştir.

Bulgular: Sıçanlar deneyin son gününde (30.Gün) travma

hatırlatıcılara maruz kaldıklarında, stres gruplarındaki anksiyete

indekslerinin kontrol grubuna göre belirgin bir şekilde arttığı

gözlemlenmiştir (P<0.001). Ayrıca, kronik FLU tedavisinin stress

gruplarında anksiyete değerlerini düşürerek geriye döndürdüğü

gözlemlenmiştir (P<0.001).

Sonuç: Bu çalışmada, stresin kaygı benzeri davranışları

arttırarak sıçan beyin hipokampüs ve frontal korteksinde M1

ekspresyon seviyesini azalttığı gözlemlenmiştir. Düşük doz

kronik FLU tedavisi ile bu etkilerin geri döndürülebileceği

öngörülmektedir.

Anahtar Kelimeler

Muskarinik reseptör, Stres, Kedi kumu, Fluoksetin, Hippokampüs, Frontal korteks

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