EFFECTS OF WATERPIPE WATER ON REWARDING, ANTINOCICEPTIVE, AND LOCOMOTOR ACTIVITY IN RATS

Waterpipe smoking (also known as shisha or hooka smoking) is a common traditional way to smoke tobacco in Middle Eastern countries, and a growing health problem in the western societies. Nicotine, the main active ingredient of tobacco, is responsible for many behavioral and psychological changes in humans and animals. However, tobacco contains hundreds of compounds that may influence the final outcomes of nicotine in humans and animals. In this study, we tested the effect of the water generated after waterpipe smoking session on conventional animal models used to study addictive and behavioral effects of nicotine. Waterpipe water was collected after extended smoking session by volunteers. Nicotine levels were analyzed using a validated High Pressure Liquid Chromatography (HPLC) method coupled with photodiode array detector, and nicotine concentration was reference point for subsequent injections. Waterpipe water was injected subcutaneously in Sprague-Dawly rats at doses range between 0.01-1.0 mg/kg, and the behavioral changes were assessed using Conditioned-Place Preference (CPP), locomotor activity, and hotplate (52 Celsius). CPP was tested in 3-compartment chamber, with two of the three compartments were differ in color and texture. 4-days protocol was used, such that rats were allowed to explore all three chambers freely between for 15 minutes on day 1; days 2 and 3 were conditioning days, such that rats were counterbalanced between drug or vehicle injections in morning or afternoon sessions; day 4 was identical to day 1. The drug was administered in the non-preferred compartment that was determined on day 1. Waterpipe water produced dose-dependent increase in CPP, which was significant after 1.0 mg/kg. Pure nicotine (used as positive control) produced significant CPP at 0.5 mg/kg. Waterpipe water (0.01-1.0 mg/kg nicotine) did not affect locomotor activity in rats (measured by beam breaks during 20-min session post injection). Moreover, waterpipe water had minimal effect on thermal nociceptive, although it decrease nociception threshold after 0.32-1.0 mg/kg at 10 minutes post-injection. These results suggest that waterpipe water is less potent than nicotine to produce CPP, and it does not affect lacomotor activity of rats. These findings support the use of waterpipe water in preclinical studies to understand the neurobiology of the rewarding effects of hooka smoking in humans.