Longitudinal magnetic resonance imaging reveals striatal hypertrophy in a rat model of long-term stimulant treatment
| Autor: | Ravi Bansal, S Xie, Christoph Kellendonk, Dominik Biezonski, Scott Gerum, Bradley S. Peterson, Jonathan Posner, Jan Hrabe, A Krivko, Jiook Cha, David N. Guilfoyle, Yunsuo Duan, R Shah, Bennett L. Leventhal |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Dextroamphetamine medicine.medical_treatment Physiology Muscle hypertrophy Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Animals Longitudinal Studies Lisdexamfetamine Dimesylate Biological Psychiatry medicine.diagnostic_test Body Weight Magnetic resonance imaging Hypertrophy Organ Size medicine.disease Magnetic Resonance Imaging Rats Neostriatum Stimulant Psychiatry and Mental health 030104 developmental biology Lisdexamfetamine Schizophrenia Behavioral medicine Original Article Central Nervous System Stimulants Psychopharmacology Psychology Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Translational Psychiatry |
| ISSN: | 2158-3188 |
| DOI: | 10.1038/tp.2016.158 |
| Popis: | Stimulant treatment is highly effective in mitigating symptoms associated with attention-deficit/hyperactivity disorder (ADHD), though the neurobiological underpinnings of this effect have not been established. Studies using anatomical magnetic resonance imaging (MRI) in children with ADHD have suggested that long-term stimulant treatment may improve symptoms of ADHD in part by stimulating striatal hypertrophy. This conclusion is limited, however, as these studies have either used cross-sectional sampling or did not assess the impact of treatment length on their dependent measures. We therefore used longitudinal anatomical MRI in a vehicle-controlled study design to confirm causality regarding stimulant effects on striatal morphology in a rodent model of clinically relevant long-term stimulant treatment. Sprague Dawley rats were orally administered either lisdexamfetamine (LDX, ‘Vyvanse’) or vehicle (N=12 per group) from postnatal day 25 (PD25, young juvenile) until PD95 (young adult), and imaged one day before and one day after the 70-day course of treatment. Our LDX dosing regimen yielded blood levels of dextroamphetamine comparable to those documented in patients. Longitudinal analysis of striatal volume revealed significant hypertrophy in LDX-treated animals when compared to vehicle-treated controls, with a significant treatment by time point interaction. These findings confirm a causal link between long-term stimulant treatment and striatal hypertrophy, and support utility of longitudinal MRI in rodents as a translational approach for bridging preclinical and clinical research. Having demonstrated comparable morphological effects in both humans and rodents using the same imaging technology, future studies may now use this rodent model to identify the underlying cellular mechanisms and behavioral consequences of stimulant-induced striatal hypertrophy. |
| Databáze: | OpenAIRE |
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