NICOTINE AND METHYLPHENIDATE CHORNIC EXPOSURE ON ADULT CANNABINOID RECEPTOR AGONIST (CP 55,940) PLACE CONDITIONING IN MALE RATS

A problematic connection has been reported between those who use nicotine related products alone or in combination with ADHD medications, like methylphenidate (MPH), in late childhood or early adolescence and the increased likelihood of later marijuana abuse in adulthood. Pre-clinical studies have found that the use of nicotine during the early adolescence period produces enduring changes to the endocannabinoid system in the brain. Since CB agonists, like marijuana, exert their effect through the eCB system, it is possible that early nicotine use may alter the rewarding nature of CB agonists in adulthood. In addition, MPH has also been shown to increase nicotine self-administration and abuse related behaviors of nicotine in rats. Thus, the current study consisted of two experiments looking at the effects of early nicotine and methylphenidate exposure on adult CB-agonist place conditioning in rats. In the first experiment, rats were pre-exposed to either saline or nicotine (0.16, 0.32, or 0.64 mg/kg) from PD 31 to PD 40. On PD 60, rats began a 13-day biased CPP procedure with the CB agonist, CP 55,940 (10, 20 or 30 μg/kg), or vehicle. No significant group differences were found, suggesting that early nicotine exposure does not influence the rewarding nature of CB agonists. Additional individual subgroup comparisons were conducted to determine if any subgroups significantly differed from 0 or no mean change in preference from preconditioning to testing. These analyses revealed that rats pre-exposed to the moderate (0.32 mg/kg) dose of nicotine showed a significant aversion to the high (30 μg/kg) dose of CP 55,940, suggesting that early nicotine exposure may reduce the rewarding nature of CB agonists in adulthood. In the second experiment, rats were pre-exposed to either saline or MPH (0.5, 2, 0r 5 mg/kg) from PD 21 to PD 30. Similar to the first experiment, rats began a 13-day biased CPP procedure on PD 60 with CP 55,940 (10, 20 or 30 μg/kg) or vehicle. Rats conditioned with the moderate (20 μg/kg) dose of CP 55,940 showed a significant preference for the CB agonist as compared to rats conditioned with the high (30 μg/kg) dose of CP 55,940. CP 55,940 exposed rats did not significantly differ from control rats. There was no significant effect of MPH or a MPH x CP 55,940 interaction, suggesting that early MPH exposure does not alter the rewarding nature of CB agonists in adulthood. Together these findings suggest that early nicotine, but not MPH, exposure may influence the rewarding nature of CB agonists in adulthood, suggesting an additional risk factor of early nicotine use. However, future studies should evaluate the effects of persistent nicotine and MPH exposure starting in early adolescence or childhood through adulthood to determine whether the effects of nicotine and MPH are altered if use is continued into adulthood