Adolescent d-amphetamine treatment in a rodent model of attention deficit/hyperactivity disorder: impact on cocaine abuse vulnerability in adulthood

作者：Jordan Chloe J; Lemay Carley; Dwoskin Linda P; Kantak Kathleen M^*

来源：Psychopharmacology, 2016, 233(23-24): 3891-3903.

DOI：10.1007/s00213-016-4419-2

• Adolescence
• Attention deficit/hyperactivity disorder
• Cocaine self-administration
• d-Amphetamine
• Spontaneously hypertensive rat

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.

• 出版日期2016-12