Contraceptive Hormone Influences on the Role of Primary Reinforcement and Reinforcer-enhancement in Nicotine Self-administration

Hormonal contraceptives contain a synthetic estrogen (e.g., ethinyl estradiol/EE) and/or a synthetic progestin (e.g., levonorgestrel/LEVO) and can exacerbate nicotine intake. However, whether altered intake reflects changes in nicotine reinforcement or enhancement by nicotine of co-occurring reinforcers is unknown. This reinforcer-enhancement effect is evidenced in rats when nicotine self-administration is increased by the presence of a visual stimulus (VS) reinforcer. This dissertation examined the effects of EE and LEVO on nicotine reinforcement and reinforcer-enhancement in ovary-intact female Sprague-Dawley rats. Rats were implanted with a jugular catheter and assigned to receive daily injections of EE (Vehicle, 0.125 [Low], or 0.18 [High] μg/day; Experiment 1) or LEVO (Vehicle, 0.3 [Low], or 0.6 [High] μg/day; Experiment 2) throughout self-administration. Rats were assigned to respond for 0.03 or 0.06 mg/kg/inf nicotine or saline during two phases. Each consisted of ten sessions on a Variable Ratio (VR)-3 schedule: the Infusion Only phase, responding only for their assigned solution, and the Infusion+VS phase, responding for their assigned solution and a 30-second VS. The Infusion+VS phase also included five sessions on a Progressive Ratio (PR) schedule. In Experiment 1, 0.06 but not 0.03 mg/kg/inf nicotine maintained self-administration during the Infusion Only phase – self-administration was unchanged by EE. EE did alter self-administration during the Infusion+VS phase. For Infusion+VS VR3 sessions, Vehicle rats responded more for 0.03 than 0.06 mg/kg/inf nicotine or saline, while Low EE rats responded more for 0.03 and 0.06 mg/kg/inf nicotine than saline. High EE rats did not self-administer any nicotine dose. For Infusion+VS PR sessions, Vehicle and Low EE rats self-administered 0.03 and 0.06 mg/kg/inf nicotine more than saline. In Vehicle but not Low EE rats, 0.03 mg/kg/inf nicotine maintained greater self-administration than 0.06 mg/kg/inf nicotine. High EE rats only self-administered 0.06 mg/kg/inf. In Experiment 2, we replicated Experiment 1 insofar that 0.06 but not 0.03 mg/kg/inf nicotine without the VS maintained self-administration. Responding during the Infusion+VS phase replicated that of Vehicle rats in Experiment 1. LEVO did not alter self-administration during any phase. EE and LEVO disrupted normal estrous cycling, and EE increased uterine weights. Thus, our EE and LEVO doses were physiologically effective.Advisor: Rick A. Bevins