Impact of Menthol on Oral Nicotine Consumption in Female and Male Sprague Dawley Rats

Comparing taste preference for menthol stereoisomers in adolescent Sprague–Dawley rats.

“…Prior to our study, all menthol taste-preference work has been done with (−)-menthol. Our data aligns with a previous report showing that 100 mg/L of (−)-menthol produces taste aversion in adult rats (Bagdas et al, 2020), however we show here that 50 mg/L is aversive, suggesting differences in menthol preference for at least across age. We cannot make any conclusions on (+)-menthol adult menthol preferences since this has not been.…”

“…Second, we sought to avoid carryover effects by increasing the dose of menthol over a log range (10-100 mg/L) so that any carryover effects from drinking a low-concentration solution to a much higher one (10-50 and 50-100), would be negligible in the face of the higher concentrations. Providing these concentrations in a counterbalanced order would more likely lead to carryover effects, especially in the case of a 100-10 mg/L shift, knowing that the former dose has been shown to be aversive in adult rats (Bagdas et al, 2020). Additionally, providing these concentrations in a counterbalanced order would likely significantly increase the variability and make it more difficult to detect sex and stereoisomer effects (Tordoff et al, 2008).…”

“…From P33 to P41, rats were given a choice between water and escalating doses of menthol (0, 10, 50, and 100 mg/L), with the dose escalating every 2 days. The doses selected in these studies are similar to other preclinical rat and mouse studies (Bagdas et al, 2020;Fait et al, 2017;Fan et al, 2016;Wickham et al, 2018), and at concentrations comparable to those seen in oral tobacco products (Celebucki et al, 2005;Fan et al, 2016). To avoid potential side biases, the bottle locations were alternated daily, with food placement equidistant from each bottle (Nesil et al, 2011;Yoneyama et al, 2008).…”

“…Preclinical studies support the epidemiological evidence that menthol exacerbates tobacco smoking (Wickham, 2019). Indeed, preclinical studies have demonstrated that adding menthol to a nicotine solution, which is bitter, increases oral nicotine consumption in mice (Fait et al, 2017; Fan et al, 2016) and rats (Bagdas et al, 2020; Wickham et al, 2018). Moreover, menthol can reduce respiratory irritation responses to smoke irritants (Willis et al, 2011).…”

Modeling drug exposure in rodents using e-cigarettes and other electronic nicotine delivery systems

“…Additionally, menthol increases oral nicotine consumption in male rats (Haskins et al, 2018). While some groups report potential sex-specific responses to menthol (Alsharari et al, 2015;Bagdas et al, 2019), others suggest that menthol alters reward circuitry in both sexes (Henderson et al, 2017;Henderson et al, 2016). Furthermore, menthol can reduce the aversive effects of nicotine in a two-bottle choice model of conditioned taste aversion in adolescent rats of both sexes (Harris et al, 2019), suggesting that certain flavors may facilitate increased consumption of nicotine in young adults.…”