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#. *. *. Wistar Kyoto and Wistar Rats Differ in Nicotine-Induced Conditioned Taste Avoidance. Jason B. Tanenbaum 1 , Lisa M. Bollwage 1 and Anthony S. Rauhut 1,2 , Department of Psychology 1 and Neuroscience Program 2 , Dickinson College, Carlisle, PA. Abstract. Purpose. Results.
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# * * Wistar Kyoto and Wistar Rats Differ in Nicotine-Induced Conditioned Taste Avoidance Jason B. Tanenbaum1, Lisa M. Bollwage1 andAnthony S. Rauhut 1,2, Department of Psychology1 and Neuroscience Program2, Dickinson College, Carlisle, PA Abstract Purpose Results Discussion The Wistar-Kyoto (WKY) rat is an animal model of clinical depression. Previous research in the laboratory suggests that WKY rats are less responsive to the rewarding and locomotor effects of nicotine compared to Wistar rats. Such strain differences may be due to general, non-specific strain differences in the neuropharmacological processing of nicotine. Thus, the present experiment examined if WKY rats were less responsive to another neuropharmacological aspect of nicotine compared to Wistar rats. Specifically, the present study examined if WKY rats were less responsive to the avoidance properties of nicotine compared to Wistar rats, as assessed using the conditioned taste avoidance (CTA) paradigm. WKY and Wistar rats underwent a CTA procedure which consisted of 4 alternating drug and non-drug sessions (counterbalanced). Drug sessions consisted of 15-min access to saccharin (0.15%) followed immediately by an injection (s.c.) of either vehicle (physiological saline) or nicotine (0.2, 0.4 or 0.8 mg/kg). It was found that WKY rats that received the lowest nicotine dose (0.2 mg/kg) did not differ from WKY rats that received the vehicle (i.e., no CTA). However, WKY rats that received the two highest nicotinedoses (0.4 and 0.8 mg/kg) drank less than the WKY rats that received the vehicle on several sessions (i.e., CTAs). Only the Wistar rats that received the highest nicotine dose (0.8 mg/kg) drank less than Wistar rats that received the vehicle on several sessions. Thus, WKY rats were more responsive to the avoidance properties of nicotine compared to Wistar rats. • The present experiment found that nicotine dose-dependently produced a CTA in WKY rats. Specifically, the two highest nicotine doses (0.4 and 0.8 mg/kg) yielded a CTA whereas the lowest nicotine dose (0.2 mg/kg) did not. • Only highest nicotine dose (0.8 mg/kg) yielded a CTA in the Wistar rats. • Collectively, these results suggest that the WKY rats are more responsive to the avoidance properties of nicotine relative to the Wistar rats. • These results are consistent with prior studies that have shown that WKY rats are responsive to other drugs of abuse (e.g., alcohol; Cailhol and Morméde, 2001). • Moreover, these results suggest that the previously-observed deficit in nicotine conditioned place preference by the WKY rats is not due to a general, unresponsiveness to the behavioral actions of nicotine or a general deficit in learning. • Rather, the results of the present experiment, when viewed in tandem with the results of previous unpublished research from the laboratory, indicate that WKY rats display a specific deficit in reward-based learning with respect to nicotine. • This interpretation is consistent with previous studies suggesting that WKY display anhedonia under certain conditions (Jiao, Pare, and Tejani-Butt, 2003; Pare, 2000). • The purpose of the present study was to examine if WKY rats were less responsive to the avoidance properties of nicotine compared to Wistar rats, as assessed by the conditioned taste avoidance (CTA) paradigm. Consumption Data Prediction • If WKY rats are unresponsive to the behavioral actions of nicotine, then WKY rats are predicted to display a less robust CTA relative to Wistar rats. • If, however, WKY rats are responsive to the behavioral actions of nicotine, then WKY rats are predicted to display a CTA similar to or more than Wistar rats. • Left Panel. The two highest nicotine doses (0.8 and 2.0 mg/kg) produced a CTA on several sessions and the test session in the WKY rats. (* = 0.8 mg/kg nicotine vs. vehicle; # = 0.4 mg/kg nicotine vs. vehicle), p < .05. • Right Panel. The highest nicotine dose (0.8 mg/kg) produced a CTA on the test session only in the Wistar rats (* = 0.8 mg/kg nicotine vs. vehicle), p < .05. WKY Wistar Methods References Acclimation 5 Days Introduction Cailhol, S. & Mormède, P. (2001) Conditioned taste aversion and alcohol drinking: Strain and gender differences. Journal of Studies on Alcohol,63, 91-99. Paré, W.P. (2000). Investigatory behavior of a novel conspecific by wistar kyoto, wistar, spraugue-dawley rats. Brain Research Bulletin, 53, 759-765. Xilu, J., Paré, W.P., & Butt-Tejani, S. (2003). Strain differences in the distribution of dopomine transporter sites in rat brain. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 27, 913-919. • Previous research suggests that Wistar Kyoto rats are an animal model of clinical depression, exhibiting less motor activity and greater anhedonia compared to other rat strains (Pare, 2000). • Previous unpublished research from the laboratory has found that WKY rats failed to display a nicotine conditioned place preference or show alterations in nicotine-induced changes in locomotor activity compared to Wistar rats. These results suggest that WKY rats are less responsive to the rewarding and locomotor properties of nicotine compared to Wistar rats. • However, the finding that WKY rats failed to display a nicotine conditioned place preference or nicotine-induced alterations in locomotor activity may suggest that WKY rats were unresponsive to any behavioral actions of nicotine. 24 h Initial Water Restriction 1 Session 15 min access to tap water following water removal 24 h Pretest 1 Session 15 min access to saccharin (0.15 %) Weight Data 24 h Acknowledgements Conditioning 8 Sessions—Alternating Drug and NonDrug Sessions (counterbalanced) Drug Sessions: 15 min access to saccharin (0.15%) followed immediately by an injection (s.c) of vehicle (physiological saline) or nicotine (0.2, 0.4 or 0.8 mg/kg) NonDrug Sessions: 15 min access to tap water in the absence of any injections This research was supported by a National Institutes of Health grant (DA019866), awarded to A. S. Rauhut. We would like to especially thanks Professor Rauhut for his guidance and support during this experiment. 48 h after last drug session • Left Panel. Displays weights of WKY rats over 6 sessions. No significant group differences were observed, p > 0.05. • Right Panel. Displays weights of Wistar rats over 6 sessions. Although no individual group differences existed, Wistar rats were heavier and gained more weight over time compared to WKY rats, ps < 0.05. Test 15 min access to saccharin (0.15%) in the absence of any injections