Effects of nicotine on depressive-like behavior and hippocampal volume of female WKY rats

Abstract

The observed high incidence of smoking amongst depressed individuals has led to the hypothesis of 'self medication" with nicotine in some of these patients. The inbred Wistar-Kyoto (WKY) rats exhibit depressive-like characteristics as evidenced by exaggerated immobility in the forced swim test (FST). One aim of this study was to investigate whether nicotine may have an antidepressant-like effect in these animals. Moreover, because of human postmortem studies indicating a reduction of the hippocampus volume in depressed patients, it was of interest to determine whether such an anatomical anomaly may also be manifested in WKY rats and whether it would be affected by chronic nicotine treatment. Adult female WKY and their control Wistar rats were administered nicotine consecutively (0.2 mg/kg, i.p., once or twice daily for 14 days) and their activity in an open field, as well as their immobility in FST were assessed either 15 min or 18 h after the last injection. Another set of animals was treated twice daily with 0.2 mg/kg nicotine for 14 days and sacrificed on day 15 for stereological evaluation of the hippocampal volume. When tested 15 min after the last injection, once or twice daily nicotine exacerbated the immobility in the FST in WKY rats only. When tested 18 h after the last injection, only twice daily nicotine treatment resulted in less immobility in the FST in WKY rats. Open field locomotor activity was not affected by any nicotine regimen. WKY rats had significantly less hippocampal volume (approximately 20%) than Wistar rats which was not altered by nicotine. These findings further validate the use of WKY rats as an animal model of human depression and signify the importance of inherent genetic differences in final behavioral outcome of nicotine.

Fig. 1

Effects of chronic nicotine treatment on the forced swim test (1A) and open field locomotor activity (1B) of female Wistar and WKY rats. The animals were treated once daily with 0.2 mg/kg nicotine for 14 consecutive days and were evaluated for LCA and FST, 15 min after the last injection. Values are mean ± SEM. N=8/group, *p<0.05, **p<0.01

Fig. 2

Effects of chronic nicotine treatment on the forced swim test (2A) and open field locomotor activity (2B) of female Wistar and WKY rats. The animals were treated once daily with 0.2 mg/kg nicotine for 14 consecutive days and were evaluated for LCA and FST, 18 h after the last injection. Values are mean ± SEM. N=8/group, **p<0.01

Fig. 3

Effects of chronic nicotine treatment on the forced swim test (3A) and open field locomotor activity (3B) of female Wistar and WKY rats. The animals were treated twice daily with 0.2 mg/kg nicotine for 14 consecutive days and were evaluated for LCA and FST, 15 min after the last injection. Values are mean ± SEM. N=8/group, *p<0.05, **p<0.01

Fig. 4

Effects of chronic nicotine treatment on the forced swim test (4A) and open field locomotor activity (4B) of female Wistar and WKY rats. The animals were treated twice daily with 0.2 mg/kg nicotine for 14 consecutive days and were evaluated for LCA and FST, 18 h after the last injection. Values are mean ± SEM. N=8/group, *p<0.05, **p<0.01

Fig. 5

The total left hippocampal volume in Wistar and WKY rats following 14 consecutive days of daily treatment with nicotine or saline. Rats were injected twice daily with 0.2 mg/kg nicotine and were perfused for histological studies 18 h after the last injection. N=8/group, *p<0.05