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.