Abstract
Methylphenidate (MPD) is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD). Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if MPD administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered MPD doses (1.3, 2.7 and 5 mg/Kg) to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3 mg/Kg MPD; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum (MS), an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5 mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the MS the sparse tyrosine hydroxylase fibers did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons.
Highlights
Attention deficit hyperactivity disorder (ADHD) is a developmental disorder affecting an estimate of 3--5% of children worldwide
This study aims to clarify the relationship between neural activity in septal areas and MPD treatment
Our results emphasized the specificity of MPD treatment and the relevance of CR neurons within septal areas
Summary
Attention deficit hyperactivity disorder (ADHD) is a developmental disorder affecting an estimate of 3--5% of children worldwide. In the 60--80% of cases, symptoms persist into adolescence and adulthood (Polanczyk et al, 2007). The aetiology of this disorder is not fully understood, but current belief points to alterations in the dopaminergic system underling the onset of the disease. Mutations and polymorphisms in the dopamine transporter (DAT) have been associated with ADHD (Miller and Madras, 2002). Metylphenidates activates calretinin neurons an increase in DAT density up to 70% in ADHD patients compared to healthy volunteers (Dougherty et al, 1999). Reduced dopamine activity has been reported in striatal areas of ADHD patients (Volkow et al, 2007). Alterations in the dopamine receptor D1 mediated neurotransmission in specific brain regions have been described in animal models of ADHD, such as the spontaneously hypertensive rats (SHR; Russell et al, 1995; Ohno et al, 2012)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
