|M.Sc Student||Havkin Evgeny|
|Subject||The Effects of Methylphenidate on Different Types of|
|Department||Department of Medicine||Supervisor||Dr. Avraham Avital|
|Full Thesis text|
Attention is a highly complex neurophysiologic mechanism, which produces filtration of sensory data inputs and is responsible for cognitive resource allocation. One of the most difficult problems in society is the rise in the prevalence of attentional deficit hyperactivity disorder (ADHD). The attentional system can be subdivided into several types of attention; though vast majority of the current diagnosis is concentrated on one particular subtype (sustained attention). Sustained attention can be measured using different paradigms; one that we recently proposed is the ASAT (auditory sustained attention test) using pre-pulse inhibition (PPI). We noticed that the PPI experiments, aimed to measure sensory-motor gating or suggested as indication of positive symptom in animal models for schizophrenia. Importantly, there is a lack of unified protocols.
Methylphenidate (MPH) is a Psychostimulant, and is usually the drug of choice in the treatment ADHD, its mode of action is not fully understood. MPH is generously prescribed, in spite of the narrow diagnostic range, and the incomplete understanding of this pharmacotherapy. There is also a rise in one time users among college student ("pre-exam"), without a comprehensive body of knowledge regarding the effects of MPH Administration regime.
In the current series of experiments, we addressed the following major hypotheses:
1. The formation of a systematic PPI protocol will establish an auditory sustained attention test.
2. MPH will affect differently different types of attention.
3. MPH will affect differently when taken acutely or chronically.
4. The administration regime of MPH will exert different effects on the various types of attention.
5. Acute or chronic MPH administration will lead to different effects on the expression of D1/D5 receptors in the striatum.
Thus, we performed a careful analysis of the existing protocols of PPI, and we established the most adequate protocol to serve as an auditory sustained attention test (ASAT). Next, we measured the behavioral effects of methylphenidate on 3 different types of attention: (i) ASAT; (ii) object recognition; (iii) social attention. Moreover, we compared acute vs. chronic MPH administration. Lastly, we analyzed the effects of MPH on the expression of dopamine D1 and D5 receptors in the striatum.
Our results suggest a way to better PPI protocols, and to form a protocol that serves as ASAT. We found that acute administration of MPH led to impaired performance in all 3 types of attention that we examined. However, chronic administration of MPH improved both ASAT and social attention performance. Lastly, we are the first to show an effect of MPH on the expression of D1 and D5 receptors in the striatum. Specifically, we found a decreased expression of D5R following an acute administration of MPH.
Together, in this study we provided thoroughly acquired methodological guidelines to performing ASAT. We also provided evidence, so far unseen in the literature, that MPH affects differentially several types of attention, and also have diverging effects in the acute and chronic modes of administration. Targeting the striatum, we suggest a possible mechanism by which methylphenidate can disrupt attentional processes when acutely administered.