Strain and Sex Matters: Differences in Nicotine Self-Administration Between Outbred and Recombinase-Driver Transgenic Rat Lines

• Published in: Experimental and clinical psychopharmacology 2021-08, Vol.29 (4), p.375-384
• Main Authors: Leyrer-Jackson, Jonna M., Overby, Paula F., Bull, Amanda, Marusich, Julie A., Gipson, Cassandra D.
• Format: Article
• Language: English
• Subjects: Animal; Animal Sex Differences; Animal Strain Differences; Animals; Conditioning, Operant; Drug Self Administration; Female; Male; Nicotine; Nicotine - administration & dosage; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Rats, Transgenic; Recombinases; Self Administration
• ISSN: 1064-1297; 1936-2293; 1936-2293
• DOI: 10.1037/pha0000376

Preclinical studies of nicotine self-administration provide important value for the field as they are highly rigorous, controlled, can be conducted quickly, and are generalizable to humans. Given the translational value of the nicotine self-administration model, and the relatively new guidelines of the National Institutes of Health to include sex as a biological variable, strain and sex differences in nicotine acquisition were examined here in two outbred rat strains. Sprague-Dawley (SD) and Long-Evans (LE; wildtype and cholinergic acetyltransferase cre-recombinase transgenic) rats of each sex were implanted with indwelling intravenous jugular catheters. Rats were trained to self-administer nicotine (0.02 mg/kg per infusion, paired with contingent light + tone stimuli). Acquisition criteria were set at a minimum active:inactive response ratio of 2:1 and a minimum of 10 infusions per session, both of which had to be met for a minimum of 10 sessions. Across 10 sessions, male SD rats self-administered significantly more nicotine than female SD rats (p < .05), indicating a sex difference in this strain. LE females self-administered more nicotine than SD females indicative of a strain difference between females (p < .05). SD males increased nicotine infusions across sessions compared to LE males and SD females (p < .05). No strain or sex differences were observed in the number of sessions to reach criteria. No differences between wildtype and transgenic LE rats were observed. These results demonstrate sex and strain differences in nicotine self-administration between SD and LE rats and may lend insight into development of other nicotine self-administration models, where sex and strain may impact acquisition. Public Health Significance It is important for preclinical animal models of nicotine addiction to approximate patterns of nicotine use in humans, taking sex into account. Further, choice of strain may directly influence behavioral outcomes in preclinical nicotine models, thus it is important to characterize strain differences in nicotine intake. This study highlights sex and strain differences that provide beneficial insight into acquisition of nicotine self-administration behavior in preclinical models.