Strain-dependent effects of acute, chronic, and withdrawal from chronic nicotine on fear conditioning

Abstract

The effects of nicotine on cognitive processes such as learning and memory may play an important role in the addictive liability of tobacco. However, it remains unknown whether genetic variability modulates the effects of nicotine on learning and memory. The present study characterized the effects of acute, chronic, and withdrawal from chronic nicotine administration on fear conditioning, somatic signs, and the elevated plus maze in 8 strains of inbred mice. Strain-dependent effects of acute nicotine and nicotine withdrawal on contextual fear conditioning, somatic signs, and the elevated plus maze were observed, but no association between the effects of acute nicotine and nicotine withdrawal on contextual fear conditioning were observed, suggesting that different genetic substrates may mediate these effects. The identification of genetic factors that may alter the effects of nicotine on cognition may lead to more efficacious treatments for nicotine addiction.

Fig. 1

Strain-dependent differences in the effects of acute nicotine on contextual fear conditioning (a) and cued fear conditioning (b). Acute nicotine enhanced contextual fear conditioning in 6 of 8 strains. Error bars indicate ± SEM, (*) indicates p <0.05 compared to saline treated mice from each respective strain

Fig. 2

Strain-dependent differences in the effects of nicotine withdrawal on contextual fear conditioning (a) and cued fear conditioning (b). Nicotine withdrawal disrupted contextual fear conditioning in 5 of 8 strains. Error bars indicate SEM, (*) indicates p <0.05 compared to saline treated mice from each respective strain

Fig. 3

Strain-dependent differences in plasma nicotine and cotinine following 0.09 mg/kg acute or 6.3 mg/kg/d chronic nicotine administration. a Acute plasma cotinine was significantly different between D2 mice and all strains other than 129 (*). BALB mice also exhibited higher plasma cotinine levels relative to A (#) and C3H mice ($). b Chronic plasma nicotine levels differed between D1 and BALB mice (*). Chronic plasma cotinine levels differed between 129 mice and all strains other than D1 (#), between D1 mice and all strains other than 129 (^), between D2 and all strains other than A mice ($), and between CBA and C57 mice (&)