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.

Cognitive and emotional behavioural changes associated with methylphenidate treatment: a review of preclinical studies

“…At a lower dose, long-term MPH treatment (1 mg/kg i.p.) increased dendritic length and complexity in anterior cingulate cortex (Zehle et al 2007) (see Table 1), a region known to play a key role in attention and executive functions (Swanson et al 2010). These findings are consistent with reports that other DA stimulants administered at therapeutic doses promote long-term dendritic growth (Diaz Heijtz et al 2003), and have interesting implications for enduring psychostimulant effects on synaptic organization.…”

Early adversity, hypocortisolism, and behavior problems at school entry: A study of internationally adopted children

“…This does not mean that chronic stress during the first years of life is uninvolved in the pathophysiology of attention problems and more generally in executive function deficits (Arnsten, 2009). Indeed, there is good evidence that reductions in the quality of care received by young mammals impairs the development of frontal brain regions (Bock et al, 2005) and that methylphenidate fosters recovery of function following stress, consistent with its effects on children diagnosed with ADHD (Zehle et al, 2007). It is possible that early adversity induced hyperactivity of the HPA axis both stimulates a down-regulation of the HPA axis and damages the development of neural systems that support attention regulation.…”

Methylphenidate Exerts Dose-Dependent Effects on Glutamate Receptors and Behaviors

“…In addition to enhancing cognitive function, MPH is able to combat stress (57). Chronic or severe stress is a trigger for many mental illnesses (58).…”