Methylphenidate partly normalizes inattentiveness, brain hypofunction and synaptic wiring: Functional imaging and neuroanatomical analysis in a novel animal model for ADHD
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1
Otto-von-Guericke University Magdeburg, Institute of Biology, Germany
Early stressful experience in degus (Octodon degus) can induce behavioural changes such as hyperactivity and reduced attention towards familiar vocalizations. These behavioural changes are paralleled by altered dopaminergic function, disturbed development of synaptic connectivity in the prefrontal anterior cingulate cortex (ACd) and reduced brain activity in a number of brain areas. Since these changes are reminiscent of symptoms of the Attention-Deficit Hyperactivity Disorder (ADHD), we studied the effects of acute and chronic methylphenidate (MP) treatment on behavior, brain activity, and brain morphology.
Degu pups were stressed by one hour daily parental separation from postnatal day (PND) 1 to 21. On PND 22 degu pups were tested for hyperactivity in a classical open field test and attention deficit in a modified version of the open field test, where the pups were exposed to familiar vocalisations. In parallel, brain activity was measured by applying the 2-fluoro-2-deoxyglucose (2-FDG) technique. Additionally, dendritic spine densities and dendritic length of pyramidal neurons in the ACd were quantified using the Golgi-Cox staining technique.
We found that acute treatment with low doses of MP (1mg/kg) lead to a normalization of the behavioral deficits. Moreover, in the stressed animals acute MP treatment partly restored brain activity in prefrontal brain areas but not in sensory areas such as the auditory cortex.. On the morphological level we found that subchronic prepubertal treatment with 1mg/kg MP restored synaptic density in the ACd of hyperactive animals.
Our results show that early stress experience in degus leads to behavioral and brain functional deficits that are similar to symptoms of ADHD in humans and which can be partly restored by treatment with methylphenidate. These findings reveal that early separation stress in degus may provide a suitable animal model to study the brain functional deficits underlying behavioral disorders such as ADHD.
Conference:
41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009.
Presentation Type:
Poster Presentation
Topic:
Poster presentations
Citation:
Bock
J,
Zehle
S and
Braun
K
(2009). Methylphenidate partly normalizes inattentiveness, brain hypofunction and synaptic wiring: Functional imaging and neuroanatomical analysis in a novel animal model for ADHD.
Conference Abstract:
41st European Brain and Behaviour Society Meeting.
doi: 10.3389/conf.neuro.08.2009.09.097
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Received:
08 Jun 2009;
Published Online:
08 Jun 2009.
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Correspondence:
Joerg Bock, Otto-von-Guericke University Magdeburg, Institute of Biology, Magdeburg, Germany, joerg.bock@ovgu.de