The Impact of Chronic Early Administration of Psychostimulants on Brain Expression of BDNF and Other Neuroplasticity-Relevant Proteins

Frequently, healthy individuals, children, and students are using stimulants to treat attention deficit hyperactivity disorder (ADHD)-like symptoms or to enhance cognitive capacity, attention and concentration. Methylphenidate, the most common treatment for ADHD, similarly to cocaine, blocks the dopamine reuptake, leading to increase in dopamine level in the synaptic cleft. Brain-derived neurotrophic factor (BDNF) and other neuroplasticity-relevant proteins have a major role in cellular plasticity during development and maturation of the brain. Young Sprague Dawley rats (postnatal days (PND) 14) were treated chronically with either cocaine or methylphenidate. The rats were examined behaviorally and biochemically at several time points (PND 35, 56, 70, and 90). We found age-dependent, but stimulant-independent, alterations in the mRNA expression levels of microtubule-associated protein tau, doublecortin, and synaptophysin. The PND 90 rats, treated with methylphenidate at an early age, exhibited increased BDNF protein levels in the prefrontal cortex compared to the saline-treated group. Despite the treatment effects at the biochemical level, cocaine and methylphenidate treatments at an early age had only minor effects on the behavioral parameters measured at older ages. The biochemical alterations may reflect neuroprotective or neuroplastic effects of chronic methylphenidate treatment at an early age.