Nikotin tercih eden ve etmeyen sıçan soylarında lokomotor aktivitenin araştırılması
Küçük Resim Yok
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
GİRİŞ ve AMAÇ : Nikotin bağımlılığına yol açan temel yolaklar ile lokomotor aktiviteyi oluşturan mekanizmalar benzerdir. Laboratuvarımızda seçici tohumlama yöntemi ile nikotin tercih eden (T) ve nikotini tercih etmeyen (nT) sıçan soyları oluşturulmuştur. Kronik nikotin uygulaması ile uyarılan lokomotor aktivite, nukleus akumbenste artmış dopamin salgısının davranışsal bir göstergesi olarak kabul edilmektedir. Bu çalışmada amacımız T (nikotin tercih eden) ve nT (nikotin tercih etmeyen) sıçan soylarında, akut ve kronik nikotin uygulamasının lokomotor aktivite üzerine etkisini, cinsiyet farkını da göz önünde bulundurarak incelenmektir. YÖNTEM: Tez çalışmasında T, nT ve kontrol grubu sıçanlar, dişi/erkek, nikotin/serum fizyolojik (SF) olmak üzere 12 grup (n=9) Sprague Dawley sıçanları kullanılmıştır. Nikotin alan gruplarda subkutan enjeksiyonlar en düşük dozdan başlayıp giderek artan 4 doz şeklinde (0,1 - 0,2 - 0,4 - 0,6 mg/kg/ml serbest baz) ve her doz 14 gün süreyle uygulanmıştır. Her iki haftalık uygulamanın 1., 4., 8. ve 12. günlerinde 60 dakikalık lokomotor aktivite ölçümleri (toplam alınan yol, kafes geçiş sayısı, tekrarlayan hareketler) yapılmış, 10 dakika ve 60 dakika verileri ayrı ayrı değerlendirilmiştir. 0,1 mg/kg/ml’lık nikotin enjeksiyonunun ilk uygulamasının sonuçları akut nikotin etkisini araştırmak için kullanıldığından tek yönlü ve tek değişkenli ANOVA kullanılarak analiz edilmiştir. Kronik nikotin uygulaması verilerinin analizinde ise tekrarlayan ölçümler için ANOVA kullanılmıştır. Analiz sonucu anlamlı çıkan veriler ise post hoc Duncan testi ile değerlendirilmiştir. BULGULAR : 0,1 mg/kg akut nikotin uygulaması, dişilerde daha fazla olmak koşuluyla özellikle ilk 10 dakikada tüm hayvanlarda lokomotor aktivite üzerine depresan etkiler göstermiştir. T soyu bu dozdaki nikotinin lokomosyonu baskılayıcı etkisine en dirençli grup olarak saptanmıştır. 60 dakika verilerinde ise hiç bir grupta anlamlı baskılanma gözlenmemiştir. Kronik uygulamada üç parametrenin (toplam alınan yol, kafes geçiş sayısı, tekrarlayan hareketler) istatistiksel değerlendirmesi paralel olduğu için özette sadece toplam alınan yol sonuçları aktarılmıştır. Uygulanan tüm dozlar (p<0,001) ve her dozun ardışık uygulama günleri (p<0,001) hareketi artırmıştır. Sıçan soylarında nikotin ya da serum fizyolojik alımı farklı etkilere (p<0,001) neden olmuş, farklı nikotin dozlarına (p=0,035) verilen yanıtlar farklılık göstermiştir. Tüm nikotin dozları toplam alınan yolu artırmıştır (p<0,001). Soylar, nikotin dozu ve cinsiyet arasında etkileşim (p=0,022) bulunmuştur. Dişilerde toplam alınan yol miktarı daha fazladır (p=0,025). Cinsiyet farkı kontrol grubu hayvanlarda oldukça belirgin olduğu halde soy gruplarında bu fark ortadan kaybolmuştur. Toplamda nT grubu en az hareket eden grup iken kontrol grubu en hareketli gruptur. Düşük nikotin dozlarına (0,1 - 0,2 mg/kg) en duyarlı olan grup T grubudur (p<0,001). Nikotin dozu ve uygulama süresi arttıkça kontrol grubunun aldığı yol artmış ve en hareketli grup haline gelmiştir (p<0,001). SONUÇ: Nikotin, tüm dozlarda ve tüm soylarda spontan lokomotor aktiviteyi artırmıştır. Bağımlılığa yatkın soydan gelmek cinsiyet farkını ortadan kaldırır ve düşük doz nikotinin akut etkisine direnç sağlar. Kronik nikotin uygulamasının düşük dozlarına en duyarlı grup bağımlılığa yatkın olan soy sıçanlarıyken, yüksek nikotin dozlarına en duyarlı grup kontrol grubudur.
AIM: Main pathways that lead to nicotine addiction and mechanisms that regulate locomotor activity are similar. In our laboratory, nicotine-preferring (P) and non-preferring (nP) rat lines were produced by selective-breeding. Chronic nicotine-induced locomotor activity is considered as the behavioral indicator of increased dopamine secretion in nucleus accumbens. In this study, our aim is to examine the effect of acute and chronic nicotine administration on locomotor activity in T (nicotine-preferring) and nT (nicotine-preferring) rat lines, taking into account the gender difference. METHOD: In the thesis study, 12 groups (n=9) Sprague Dawley rats were used: T, nT and control rats, female/male, nicotine/saline (SF) rats. In the groups receiving nicotine, subcutaneous injections were administered in 4 doses (0.1 - 0.2 - 0.4 - 0.6 mg/kg/ml free base) starting from the lowest dose and increasing gradually, and each dose was administered for 14 days. On the 1st, 4th, 8th and 12th days of each two-week application, 60-minute locomotor activity measurements (total distance traveled, number of cage passes, repetitive movements) were made, and the 10-minute and 60-minute data were evaluated separately. The results of the first administration of 0.1 mg/kg/ml nicotine injection were analyzed using one-way and univariate ANOVA as it was used to investigate the acute nicotine effect. In the analysis of chronic nicotine administration data, ANOVA was used for repeated measures. The data that were significant as a result of the analysis were evaluated with the post hoc Duncan test. RESULTS: Acute nicotine administration of 0.1 mg/kg showed depressant effects on locomotor activity in all animals, especially in the first 10 minutes, provided that it is more in females. T strain was determined as the most resistant group to the locomotion suppressive effect of nicotine at this dose. In the 60-minute data, no significant suppression was observed in any group. Since the statistical evaluation of three parameters was parallel, only total path results were presented. All doses (p<0.001) and consecutive administration days of each dose (p<0.001) increased the movement. Nicotine or saline caused different effects (p<0.001) in rat lines and the responses to four nicotine doses differed (p=0.035). All nicotine doses increased the total path (p<0.001). There was a significant interaction between line, dose, and sex (p=0.022). Total path is higher in females (p=0.025). Although sex difference was evident in controls, it disappeared in selectively-bred lines. Overall, locomotor activity was lowest in nP and highest in controls. P group has the highest sensitivity (p<0.001) to low nicotine doses (0.1 - 0.2 mg/kg). As the nicotine dose and exposure duration increased, controls increased their activity and became the most active group (p<0.001). CONCLUSION: Nicotine increased locomotor activity at all doses and in all rat lines. Addiction-prone lineage eliminates sex difference and provides resistence to the acute effects of low-dose nicotine. While the group most susceptible to low doses of chronic nicotine administration is addiction-prone lineage rats , the group most susceptible to high doses of nicotine is the control group.
AIM: Main pathways that lead to nicotine addiction and mechanisms that regulate locomotor activity are similar. In our laboratory, nicotine-preferring (P) and non-preferring (nP) rat lines were produced by selective-breeding. Chronic nicotine-induced locomotor activity is considered as the behavioral indicator of increased dopamine secretion in nucleus accumbens. In this study, our aim is to examine the effect of acute and chronic nicotine administration on locomotor activity in T (nicotine-preferring) and nT (nicotine-preferring) rat lines, taking into account the gender difference. METHOD: In the thesis study, 12 groups (n=9) Sprague Dawley rats were used: T, nT and control rats, female/male, nicotine/saline (SF) rats. In the groups receiving nicotine, subcutaneous injections were administered in 4 doses (0.1 - 0.2 - 0.4 - 0.6 mg/kg/ml free base) starting from the lowest dose and increasing gradually, and each dose was administered for 14 days. On the 1st, 4th, 8th and 12th days of each two-week application, 60-minute locomotor activity measurements (total distance traveled, number of cage passes, repetitive movements) were made, and the 10-minute and 60-minute data were evaluated separately. The results of the first administration of 0.1 mg/kg/ml nicotine injection were analyzed using one-way and univariate ANOVA as it was used to investigate the acute nicotine effect. In the analysis of chronic nicotine administration data, ANOVA was used for repeated measures. The data that were significant as a result of the analysis were evaluated with the post hoc Duncan test. RESULTS: Acute nicotine administration of 0.1 mg/kg showed depressant effects on locomotor activity in all animals, especially in the first 10 minutes, provided that it is more in females. T strain was determined as the most resistant group to the locomotion suppressive effect of nicotine at this dose. In the 60-minute data, no significant suppression was observed in any group. Since the statistical evaluation of three parameters was parallel, only total path results were presented. All doses (p<0.001) and consecutive administration days of each dose (p<0.001) increased the movement. Nicotine or saline caused different effects (p<0.001) in rat lines and the responses to four nicotine doses differed (p=0.035). All nicotine doses increased the total path (p<0.001). There was a significant interaction between line, dose, and sex (p=0.022). Total path is higher in females (p=0.025). Although sex difference was evident in controls, it disappeared in selectively-bred lines. Overall, locomotor activity was lowest in nP and highest in controls. P group has the highest sensitivity (p<0.001) to low nicotine doses (0.1 - 0.2 mg/kg). As the nicotine dose and exposure duration increased, controls increased their activity and became the most active group (p<0.001). CONCLUSION: Nicotine increased locomotor activity at all doses and in all rat lines. Addiction-prone lineage eliminates sex difference and provides resistence to the acute effects of low-dose nicotine. While the group most susceptible to low doses of chronic nicotine administration is addiction-prone lineage rats , the group most susceptible to high doses of nicotine is the control group.
Açıklama
Anahtar Kelimeler
Kronik Nikotin Uygulaması, Lokomotor Aktivite, Nikotin, nT, T, Chronic Nicotine Administration, Locomotor Activity, Nicotine, nP, P
