Effects Of Chronic Nicotine On Fear Conditioning And Extinction In Rats

Object Clinical observations have shown a link for the high comorbid rate between smoking and anxiety disorders. However, little is known about the neural mechanism between them. A deficit in fear extinction in general is considered to contribute to anxiety disorders. The aim of the present study is to investigate the effects of chronic nicotine on fear extinction.Methods 1, Chronic nicotine treatment: Rats were administrated nicotine (s.c., incresing dose). Control rats were treated similarly except that normal saline was used. 2, Fear conditioning and extinction: 14 d after the last injection rats received a cued (PDC and UPDC) or contextual fear conditioning session. 24 and 48 hr after conditioning, rats received an extinction training session and an extinction test session, respectively. Percent freezing was assessed during all phases of training. 3, Locomotor activity: tested 24 hr and 13 d after the last injection, including distance, number of rearing, grooming time, and the time spent in center or peripheral area in 10 min. 4, Footshook sensitivity: tested 14 d after the last injection. The rats received unsigned foot shooks of increasing amplitude in conditioning chamber. Foot shook stopped until three response thresholds appear: noticing, flinching, and vocalizing. 5, Measurement of withdrawal symptoms: tested 24 hr and 14 d after the last injection. The somatic signs include wet dog shakes, front paw tremor, sniffing, scratches, ptosis, genital licks, tremor, and teeth chatting.Results 1, In the PDC-cued task, the nicotine group showed higher level of percent freezing than the saline group in the extinction test session, but there was no significant difference in freezing between the two groups in fear conditioning session and extinction training session. Two groups showed comparable rates of within-session extinction. 2, In the UPDC-cued task, there was no significant difference in freezing between the nicotine group and the saline group in fear conditioning, extinction training, extinction test session. The two groups also showed comparable rates of within-session extinction in extinction training and extinction test session. 3, In the contextual task, the nicotine group showed higher level of percent freezing than the saline group in the extinction training session, but there was no significant difference in freezing between the two groups in the fear conditioning session, extinction test session. Two groups showed comparable rates of within-session extinction in extinction training session. 4, 24 hr after the last injection, the nicotine group showed significant reduction of locomotor activity, but there was no significant difference tested 13d after the last injection. 5, There was no significant difference in footshook sensitivity tested 14d after the last injection. 6, there were no significant difference in nonspecific freezing to the tone and context. 7, The nicotine group showed significant withdrawal symptoms compared with the saline group 24hr after the last injection, but there were no significant difference tested 14d after the last injection.Conclusion 1, In the PDC-cued task, chronic nicotine selectively impaired the long term extinction, but has no effect on the acquisition of fear conditioning and short term extinction; 2, In the UPDC-cued task, chronic nicotine did not affect the acquisition of fear conditioning, short term extinction and long term extinction; 3, In the contextual task, chronic nicotine had no effect on the acquisition of fear conditioning or fear extinction, but enhanced the retention of fear conditioning; 4, This prior chronic nicotine-induced deficit in PDC-cued fear extinction and enhanced fear to context were not caused by changes of locomotor activity, footshook sensitivity, nonspecific freezing and withdrawal symptoms induced by chronic nicotine.