Juvenile exposure to methylphenidate and guanfacine in rats: effects on early delay discounting and later cocaine-taking behavior
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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.
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.
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.
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 (R2 = −0.4, P < 0.05) and self-administration was reduced by guanfacine treatment (0.3 mg/kg). Guanfacine significantly decreased cocaine sensitivity in both sexes.
These data suggest that MPH is effective in reducing delay discounting in both sexes. Due to both weight loss and ineffectiveness on discounting in females, guanfacine should be used only in males to reduce delay discounting and later cocaine use.
KeywordsAdolescence Cocaine Impulsive choice Intervention Prevention Substance use
The following authors contributed in the following ways: NF and CJJ wrote the MatLab programs, ran animals, and helped write the manuscript; JLL and KJN treated and ran animals; and SLA designed the study, analyzed data, and wrote the manuscript.
The authors acknowledge the support of DA-10543, DA-026485, and MH 091114 (to SLA) and the technical assistance of Ms. Britta Thompson.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
There are no competing financial interests in relation to the work described.
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