Juvenile exposure to methylphenidate and guanfacine in rats: effects on early delay discounting and later cocaine-taking behavior

Rationale Both methylphenidate (MPH), a catecholamine reuptake blocker, and guanfacine, an alpha2A agonist, are used to treat attention-deficit hyperactivity disorder (ADHD). Childhood impulsivity, including delay discounting, is associated with increased substance use during adolescence. These effects can be mitigated by juvenile exposure to MPH, but less is known about the long-term effects of developmental exposure to guanfacine in males and females. Objective This study aims to determine sex differences and dose-dependent effects of juvenile exposure to MPH or guanfacine on delay-discounting and later cocaine self-administration. Methods The dose-dependent effects of vehicle, MPH (0.5, 1, and 2 mg/kg p.o.) or guanfacine (0.003, 0.03, and 0.3 mg/kg, i.p.) on discounting were determined in male and female Sprague-Dawley rats beginning at postnatal day (P)20. At P90, the amount, motivation, and sensitivity to cocaine following early drug exposure were determined with self-administration. Results Guanfacine, but not MPH, significantly reduced weight by 22.9 ± 4.6% in females. MPH dose dependently decreased delay discounting in both juvenile males and females, while guanfacine was only effective in males. Discounting was associated with cocaine self-administration in vehicle males ( R 2 = −0.4, P