Behavioral Effects of Nicotine Withdrawal Differ by Genetic Strain in Male and Female Adolescent Rats

Gender and ethnicity are powerful predictors of initiation and maintenance of cigarette smoking in adults but less is known about their role in smoking in adolescents. Consistent with human studies, rat models also reveal sex and strain differences in response to nicotine administration. This research examined nicotine withdrawal behaviors in 96 adolescent, male and female, Sprague Dawley (SD) and Long Evans (LE) rats. Rats received seven days continuous subcutaneous infusion of saline or 3.16 mg/kg nicotine via Alzet osmotic minipumps. Behavioral observations were made before, during, and after saline or nicotine administration. Occurrences of six specific behaviors were quantified: abnormal posture or movement, abnormal grooming, whole-body shakes, ptosis, empty-mouth chewing/teeth chattering, and diarrhea. SD male and female rats that received nicotine displayed significantly more withdrawal behaviors 1 and 2 days after cessation of nicotine administration compared with rats that had received saline. LE male rats that received nicotine displayed significantly more withdrawal behaviors 1 day but not 2 days after cessation of nicotine administration compared with males that received saline. LE females showed no significant withdrawal behaviors after cessation of nicotine administration. Results indicate that nicotine withdrawal in adolescent rats depends on sex and strain.