Varying Dopamine levels effect functional connectivity in nonhuman primates

           Methylphenidate, a drug used to treat attention deficit hyperactivity disorders alters dopamine (DA) lives in the striatum. The brand name of methylphenidate is Ritalin, and this is a drug that is commonly prescribed to children who show symptoms of ADHD. Dopamine agonist is administered to patients with ADHD, because dopamine is implicated in aiding reward based learning pathways.  Dopamine transmission throughout our nervous system is implicated in large scale-neural networks that are important in cognitive functions. Methylphenidate works by blocking dopamine transporters (DAT), which are responsible for the re-uptake of the neurotransmitter dopamine. By blocking DAT, there is excess dopamine in the synaptic cleft which is able to bind to receptors and act upon it.

  This experiment explores how the increase of endogenous dopamine affects functional connections in the head caudate (hCd) and the prefrontal cortex.









   
In order to explore this connection between dopamine agonist drugs such as Ritalin and connections between brain structures, the researchers used Rhesus monkeys which are non-human primates. These monkeys were raised in a lab and were subject to behavioral training so that they can slowly be acclimated to the environments of the lab. This was done by introducing them to low static noises such as those that are present in an MRI machine. The rhesus monkeys were given an oral dose of Methylphenidate (MPH) which was delivered via an infusion of cranberry juice. Following this oral administration of MPH, the monkeys were place in an MRI machine where structural components of their nervous system was analyzed while they were under the influence of MPH medication. A PET scan was also conducted to explore the binding potential of dopamine in our nervous system. There are two variations of dopamine present endogenously in our body; D2 and D3. This PET scan seeks to identify how much of the available endogenous dopamine binds to its respective receptors.

The results of this experiment was significant because there was a relationship established between the administration of dopamine agonist drugs such as MPH and functional connections in the brain. The PET scan analysis showed that the binding potential for D2 and D3 receptors decreased by 1.37%  per mg/kg of MPH administered. This result is important, because it depicts that dopamine agonist drugs that produce extracellular DA competes with the intracellular amounts of endogenous DA present.














 The fMRI analysis of the Rhesus monkey's shows that connectivity in the head caudate (hCd) and dorso lateral pre-frontal cortex is strengthen with levels of extracellular dopamine present. This increased connectivity has shown to be the mechanism through which cognitive performance is improved in patients with ADHD.


Article: Changes in Endogenous Dopamine Induced by Methylphenidate Predict Functional Connectivity in Nonhuman Primates 

http://www.jneurosci.org/content/jneuro/39/8/1436.full.pdf