Reduced sensitivity to reinforcement in adolescent compared to adult Sprague-Dawley rats of both sexes

Rationale Adolescence is a period of considerable development of brain and behavior and is the time during which most drug use is initiated. Objective Age-dependent differences in motivated behaviors may be one of the factors that contribute to heightened vulnerability to developing substance use disorders, so we sought to compare age differences in methamphetamine (METH) and saccharin seeking. Methods Beginning during adolescence or adulthood, male and female Sprague-Dawley rats were trained to self-administer 0.1% saccharin (via liquid dipper cup) or intravenous METH at one of three doses (0.02, 0.05, 0.08 mg/kg/inf) under increasing fixed ratio schedules of reinforcement. Subsequently, responding for METH (0.02, 0.05, 0.08, or 0.1 mg/kg/inf) under progressive ratio response requirements was assessed in rats that acquired METH self-administration at the highest dose (0.08 mg/kg/inf). Results We found that adult-onset rats acquired METH self-administration more readily and exhibited higher motivation compared to adolescent-onset rats, although there were no differences in METH intake during acquisition. Adult rats also acquired saccharin self-administration more readily, but in contrast to METH, there were age and sex differences in saccharin intake driven by high levels of responding in adult females. Conclusions These findings challenge the prevailing notion that adolescents are hypersensitive to reward and instead raise questions about the potential role of methodological factors on which rodent studies often differ.