Adolescent d-amphetamine treatment in a rodent model of attention deficit/hyperactivity disorder: impact on cocaine abuse vulnerability in adulthood.
Stimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adolescents remain controversial with respect to later development of cocaine abuse. Past research demonstrated that adolescent methylphenidate treatment increased several aspects of cocaine self-administration during adulthood using the spontaneously hypertensive rat (SHR) model of ADHD. Presently, we determined effects of the alternate stimulant medication, d-amphetamine, on cocaine self-administration.



We tested the hypothesis that adolescent d-amphetamine would not increase cocaine self-administration in adult SHR, given that d-amphetamine has a different mechanism of action than methylphenidate.



A pharmacologically relevant dose of d-amphetamine (0.5 mg/kg) or vehicle was administered throughout adolescence to SHR and two control strains, Wistar-Kyoto (WKY) and Wistar (WIS). Three aspects of cocaine abuse vulnerability were assessed in adulthood after discontinuing adolescent treatments: acquisition rate and dose-related responding under fixed (FR) and progressive (PR) ratio schedules.



Adult SHR acquired cocaine self-administration faster and self-administered more cocaine across multiple doses compared to WKY and WIS under FR and PR schedules, indicating that SHR is a reliable animal model of comorbid ADHD and cocaine abuse. Relative to vehicle, SHR and WIS with adolescent d-amphetamine treatment self-administered less cocaine upon reaching acquisition criteria, and WIS additionally acquired cocaine self-administration more slowly and had downward shifts in FR and PR cocaine dose-response curves. WKY with adolescent d-amphetamine treatment acquired cocaine self-administration more quickly relative to vehicle.



In contrast to methylphenidate, adolescent d-amphetamine did not augment cocaine self-administration in SHR. Adolescent d-amphetamine treatment actually protected against cocaine abuse vulnerability in adult SHR and WIS.
Department of Psychological and Brain Sciences, Boston University, 64 Cummington Mall, Boston, MA, 02215, USA.
Chloe J
CJ
Jordan
Department of Psychological and Brain Sciences, Boston University, 64 Cummington Mall, Boston, MA, 02215, USA.
Carley
C
Lemay
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536, USA.
Linda P
LP
Dwoskin
Department of Psychological and Brain Sciences, Boston University, 64 Cummington Mall, Boston, MA, 02215, USA. kkantak@bu.edu.
Kathleen M
KM
Kantak
D000661:Amphetamine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D019970:Cocaine-Related Disorders; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar
D000697:Central Nervous System Stimulants; D000661:Amphetamine
Adolescence; Attention deficit/hyperactivity disorder; Cocaine self-administration; Spontaneously hypertensive rat; d-Amphetamine