Investigating the Interoceptive Stimulus Effects of Injected Menthol in Rats

Menthol is a commonly used tobacco constituent that also modulates nicotine reinforcement and metabolism. Little is known about the stimulus effects of menthol that mediate the behavior associated with reinforcement-learning. Our present research explored the interoceptive stimulus effects of intraperitoneally administered menthol in a drug discrimination task. For Experiment 1, Sprague-Dawley rats (N = 20) received IP menthol (0.0183 or 5 mg/kg) or vehicle. For positive sessions, rats were given menthol before receiving 8 15-s light presentations, each followed by 4-s access to liquid sucrose. For intermixed negative sessions, rats were given vehicle before receiving 8 light presentations without sucrose delivery. After 32 sessions, rats previously receiving 0.0183 mg/kg menthol were switched to 15 mg/kg menthol. After 16 sessions, the injection-to-placement-interval was switched from 5 min to 15 min for 16 additional sessions. Lastly, a subset of rats (n = 10) received nicotine discrimination training for 40 sessions, with 0.4 mg/kg nicotine pretreatment on positive days and saline on negative days. In Experiment 2, naïve rats (N = 7) received nicotine discrimination training. Later sessions assessed nicotine discrimination performance in combination with 5 mg/kg menthol or vehicle. Menthol-vehicle discrimination was not evident regardless of dose or injection-to-placement interval in Experiment 1. However, rats that underwent nicotine training developed robust drug discrimination. In Experiment 2, co-exposure with menthol or vehicle did not modulate nicotine discrimination performance. These data suggest that menthol does not acquire control of responding in a drug discrimination task. Additional research is needed to further explore the interoceptive stimulus effects of menthol and nicotine combined. Public Health Significance This study suggests that intraperitoneally administered menthol does not function as a positive feature in a drug discriminated goal-tracking task in rats. Given that there is a substantial smoking population utilizing products that contain menthol, investigating the learning mechanisms that underlie the menthol stimulus is imperative for assessing behaviors related to menthol-flavored tobacco product consumption.