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.

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.