, Volume 236, Issue 2, pp 685–698 | Cite as

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

  • Nadja Freund
  • Chloe J. Jordan
  • Jodi L. Lukkes
  • Kevin J. Norman
  • Susan L. AndersenEmail author
Original Investigation



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.


Adolescence Cocaine Impulsive choice Intervention Prevention Substance use 


Author’s contributions

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Developmental Neuropharmacology, McLean HospitalHarvard Medical SchoolBelmontUSA
  2. 2.Department of Psychiatry, McLean HospitalHarvard Medical SchoolBelmontUSA
  3. 3.Division of Experimental and Molecular PsychiatryLWL University Hospital BochumBochumGermany
  4. 4.Department of Psychiatry, Psychotherapy and Preventive MedicineRuhr-University BochumBochumGermany
  5. 5.Molecular Targets and Medications Discovery BranchNational Institute on Drug Abuse, Intramural Research ProgramBaltimoreUSA
  6. 6.Department of PsychiatryIndiana University School of MedicineIndianapolisUSA

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