Adolescent d-Amphetamine Exposure Enhances the Acquisition of Cocaine Self-Administration in Male and Female Rats

Diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) has risen drastically over the past 20 years in the United States and abroad. Amphetamine-based prescription stimulants are the most prescribed treatment for ADHD and the diversion of these drugs has also increased. Reports indicate 61% of individuals with an ADHD medication prescription have sold or shared their medication. Exposure to prescription stimulants, especially for those without an ADHD diagnosis, may increase susceptibility to drugs of abuse. The present study aimed to model ADHD medication misuse during adolescence in male and female rats. The primary dependent measure was the acquisition of intravenous cocaine self-administration. Male and female, Long-Evans rats were exposed to d-amphetamine (0.7 mg/kg, i.p.) or saline in adolescence (35-41 days old), during which locomotor activity was measured. At approximately 75 days old, animals were implanted with jugular catheters. All animals then entered a 15-day acquisition procedure with no prior operant training. Finally, following acquisition all animals responded on a progressive-ratio (PR) schedule to obtain 0, 0.1, 0.3, and 1.0 mg/kg/infusion cocaine. Animals exposed to amphetamine acquired cocaine self-administration faster than saline-exposed controls when the acquisition criterion was operationally defined as two consecutive days with 12 infusions or greater. Discrete-time hazard modeling also found amphetamine exposure to increase the likelihood of acquiring cocaine self-administration. There were no differences detected during PR testing. These data suggest that individuals with histories of prescription stimulant misuse may be at increased risk to use other drugs of abuse. Public Health Significance The percentage of young individuals using ADHD medications without an ADHD diagnosis has risen substantially in recent years. The current study modeled ADHD medication misuse in male and female rats to determine if it affected the likelihood of rats to self-administer cocaine. Results indicate that ADHD medication exposure during adolescence enhanced the acquisition of cocaine self-administration. Thus, individuals with histories of ADHD medication misuse may exhibit increased drug abuse vulnerability.