Adolescent reward system perseveration due to nicotine: Studies with methylphenidate

Previous data suggests adolescent nicotine exposure permanently disrupts reward systems. Behavioral pharmacological methods were used to assess the effects of adolescent nicotine exposure on methylphenidate (MPD) sensitivity and reward from adolescence to adulthood. For experiment one, testing was performed on adult mice exposed to nicotine (0.3 and 3.0 mg/kg, SC, M–F, b.i.d.) or saline during adolescence (PND 25–57). After a 28-day drug-free, time-off period, the locomotor effects (30 min, 30 cm traveled) of MPD (5, 10, 20, and 40 mg/kg, IP) were measured. Thereafter, mice underwent condition-place-preference testing (CPP). MPD (20 mg/kg) was paired with the subject's non-preferred side and saline with the preferred side. Conditioning sessions were conducted for 8 days with a drug-free post-test on the day following the final conditioning session. A second experiment was conducted to determine if adolescent mice respond differently to MPD compared to adult mice. The study compared adolescent mice (PND 25–46) to adult mice (PND 77–98) using identical MPD testing procedures as in experiment one. Adult subjects exposed to nicotine during adolescence behaved remarkably similar to adolescent subjects receiving only MPD. Both nicotine exposed subjects and naïve adolescents exhibited increased response to MPD's motor activating effects and a decreased response to MPD's rewarding effects. Taken together it appears that adolescent nicotine exposure retards the development of reward systems, thus, maintaining an adolescent state indefinitely, which could result in increased vulnerability to substance abuse problems throughout adulthood.