Investigation of Locomotor Activity in Nicotine Preferring and Non-Preferring Rat Lines
Project no. 22050 · Status: Kapanmış · 2020
Summary
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. Our aim is to investigate the effect of chronic nicotine administration on locomotor activity in P and nP rat lines. 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. ( Funding : BAP-TTU-2020-22050; Ethical approval : HADYEK-2020-025 ) Keywords: Chronic nicotine administration, Locomotor activity, Nicotine, nP, P