Methylphenidate treatment recovers stress-induced elevated dendritic spine densities in the rodent dorsal anterior cingulate cortex

Abstract

Exposing pups of the rodent species Octodon degus to periodic separation stress during the first three postnatal weeks leads to behavioral alterations, which include reduced attention towards an emotional stimulus and motoric hyperactivity. These behavioral changes, which are reminiscent of symptoms of attention deficit hyperactivity disorder (ADHD), are paralleled by synaptic changes in the dorsal anterior cingulate cortex (ACd), a limbic cortex region, which plays a key role in the modulation of attentional and executive functions. ADHD is typically treated with methylphenidate (MP), a drug acting on the dopaminergic system. However, the effect of chronic MP-treatment on neuronal and synaptic maturation in the developing brain is unknown. Applying the Golgi-Cox stainining technique, we tested in which way chronic MP-treatment interferes with dendritic and synaptic development in the ACd and whether this treatment can restore the stress-induced changes of neuronal connectivity. We found that chronic treatment with 1 mg/kg MP recovers stress-induced changes of spine densities in the ACd. Furthermore, MP-treatment resulted in increased dendritic length and complexity in both, stressed as well as unstressed control animals. These results indicate that synaptic reorganization as well as dendritic growth in the prefrontal cortex continue into prepuberty and are modulated by MP-treatment.