Volume 5, Issue 1
Understanding the Consequences of Early Exposure to Methylphenidate on Adult Cocaine Reward Behavior
by Dr. Arturo Zavala
Over the past two years, as an Assistant Professor at California State University, Long Beach in the Department of Psychology, I have been collaborating with Dr. Cynthia Crawford. My research focuses on investigating the short- and long-term neurochemical and behavioral effects of exposure to psychostimulant drugs across development. My interests also include examining the potential impact of early exposure to drugs on the susceptibility to abuse drugs later in life using animal models.
Dr. Crawford and I have been working on understanding the consequences of early exposure to methylphenidate on adult cocaine reward behavior in rats by using the intravenous self-administration model. We are interested in this topic because the use of prescription medications to treat psychiatric disorders in children has increased dramatically over the past three decades. The most commonly diagnosed disorder is attention deficit/hyperactivity disorder (ADHD), with prevalence estimates among children ranging from 5% to 12%. The preferred treatment for this disorder is the use of psychostimulants - methylphenidate and amphetamine - because of their effective symptomatic management. Although not approved by the Federal Drug Administration, psychostimulants are also prescribed to treat ADHD in preschool children (ages 3-5 years).
Surprisingly, the consequences of this early and extended use of psychostimulants are not well understood and there is growing concern that such exposure may increase the potential to abuse drugs. Preclinical studies with rats, for instance, demonstrate that early exposure to psychostimulants alters the rewarding value of various drugs of abuse when these animals are tested as adults. As a result of our initial collaboration, we have also found that exposure to methylphenidate during postnatal days (PD) 11-20 - a period of rat development that resembles early childhood in humans - increased cocaine self-administration when these animals were tested as adults (i.e., PD 90). These and similar findings are of substantial clinical importance and necessitate a better understanding of the consequences of early psychostimulant treatment.
This year, as a recipient of the National Hispanic Science Network’s 2011 Early Career Leadership Committee Pilot Funding Program award, we are examining whether early methylphenidate exposure enhances the escalation of cocaine self-administration in adult rats. This study uses the extended access to cocaine self-administration model because it more accurately resembles addiction in humans, as animals exhibit addictive-like behaviors (e.g., compulsive drug use and escalation of drug intake). Specifically, we are examining the effects of early methylphenidate exposure on cocaine -induced responding under extended (6 hour sessions) versus short (1 hour sessions) access conditions, to test the hypothesis that early methylphenidate promotes escalating patterns of cocaine intake.
We have also begun studying the impact early methylphenidate exposure may have on other drugs of abuse, such as nicotine and methamphetamine. Specifically, the focus of these studies is to determine if the reward value of these drugs are altered during earlier periods of development, such as adolescence. In particular, we have completed a study that used the conditioned place preference model, an animal model of drug reward, to investigate the effect of early methylphenidate pretreatment on nicotine-induced CPP in early (postnatal days (PDs) 27-34) and late (PD 41-48) adolescent rats. Our results have demonstrated that in males, early methylphenidate enhanced nicotine-induced CPP. However, the effect varied by dose of methylphenidate pretreatment and age of testing. Specifically, pretreatment with 4 mg/kg methylphenidate increased nicotine-induced CPP when animals were tested only during early, but not late adolescence. In contrast, pretreatment with 2 mg/kg methylphenidate enhanced nicotine-induced CPP during late, but not early adolescence. In females, early methylphenidate pretreatment attenuated nicotine-induced CPP regardless of dose or age of testing, as only control female rats exhibited nicotine-induced CPP. The present data adds to a growing body of evidence that early methylphenidate alters the rewarding value of various drugs of abuse.
Over the next year, my goal is to utilize the data I have collected for the submission of a larger grant proposal to the National Institute on Drug Abuse to begin examining the neurochemical changes and neuronal circuitry that that may underlie the increased sensitivity to cocaine and nicotine after early exposure to methylphenidate. I would like to thank the National Hispanic Science Network for their support, which has been instrumental in getting this research accomplished.