Abstract
Rationale
Over the past decade, adolescent cigarette smoking has been declining. However, adolescent nicotine consumption via electronic cigarettes is rapidly gaining popularity. Earlier onset nicotine use is associated with increased risk of dependence. A bidirectional relationship between nicotine and stress exists; perceived stress is a predictor for nicotine use, and stress reduction is a commonly reported reason for using nicotine.
Objectives
We assessed the prolonged impact of adolescent high-dose nicotine and/or footshock exposure on adult nicotine self-administration, anxiety-like behaviour, and hormonal responsivity.
Methods
During adolescence (postnatal day [P]28-56) male Sprague-Dawley rats were assigned to one of five groups: saline (SALPRE: 1 ml/kg, SC, every day), nicotine (NICPRE: 1 mg/kg, SC, alternating daily with saline; 14 total nicotine injections), footshock (SHOCKPRE: 8 of 0.5 s, 0.8 mA alternating sessions; saline every day), or combination nicotine and footshock (NIC+SHOCK: concurrent and alternating daily with saline, or NIC–SHOCK: alternating with saline on shock sessions). On P70, one cohort underwent spontaneous intravenous nicotine self-administration (0.03 mg/kg/infusion); another cohort was assessed for open-field behaviour (P71), then corticosterone (CORT) response to nicotine or footshock in adulthood (P72-73).
Results
Intermittent adolescent nicotine or footshock alone (NICPRE and SHOCKPRE) did not potentiate adult spontaneous nicotine intake compared to SALPRE. However, both combination groups (NIC+SHOCK, NIC–SHOCK) showed increased adult nicotine consumption without associated differences in baseline anxiety-like behaviour or CORT response.
Conclusions
Adolescent nicotine and footshock stressors have a synergistic effect on adult nicotine consumption, enhancing nicotine intake. Avenues toward reducing stress in adolescent nicotine users may provide opportunities to reduce vulnerability to adult nicotine consumption.
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Acknowledgements
We are grateful for the skilled technical support of Derek Jacklin of the Central Animal Facility.
Funding
Support for the research was provided in part by the US National Institute on Drug Abuse DA045740 and the Canadian Natural Sciences and Engineering Research Council #RGPIN-2019-05147 to JEM. The funding sources had no role in study design; data collection, analyses, or interpretation; writing; or decision to submit article for publication.
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BR and JEM designed the study; BR, AKA, APS, RE, and MS conducted the behaviour studies; MA optimized the ELISA procedures and trained BR to conduct and interpret the ELISA assays; JYK provided access to and training on shock and open field equipment; BR analyzed the data and wrote the first draft of the manuscript; JEM provided manuscript revisions; all authors have given feedback on the final manuscript and approved its submission.
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Renda, B., Andrade, A.K., Stone, A.P.S. et al. Adolescent nicotine and footshock exposure augments adult nicotine self-administration and drug-seeking without affecting baseline anxiety-like behaviour or stress responsivity in male rats. Psychopharmacology 238, 1687–1701 (2021). https://doi.org/10.1007/s00213-021-05803-0
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DOI: https://doi.org/10.1007/s00213-021-05803-0