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Vliv klomipraminu a risperidonu na učení a flexibilitu u animálního modelu obsedantně kompulzivní poruchy
Radostová, Dominika ; Stuchlík, Aleš (advisor) ; Kopřivová, Jana (referee)
Chronic sensitization of dopamine D2/D3 receptors by agonist quinpirole (QNP) induces compulsive checking behaviour in rats, which is considered an animal model of obsessive-compulsive disorder (OCD). Previous study revealed deficit in cognitive flexibility in QNP sensitized rats. This thesis focused on determining if this cognitive flexibility deficit is ameliorated by co-administration of clomipramine (CMI), risperidone (RIS) or combination of both (CMI+RIS) to QNP treatment. Aversively motivated active place avoidance task on a Carousel maze with reversal was used. The number of entrances into a to-be-avoided shock sector was evaluated as measure of performance. Six treatment groups were used: control group, QNP group, CMI group, QNP/CMI combination, QNP/RIS combination and QNP/CMI/RIS combination. Surprisingly, when compared alone, significantly worse acquisition was observed for QNP group compared to control group. However, similarly to previous study, QNP group had a worse performance in a first reversal session compared to control group. When all groups were compared, only QNP/CMI group had worse initial learning compared to control group. In reversal learning, only QNP treated group had a significantly more entrances than control group in first reversal session. Results suggest that co-treatment...
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Hippocampus Dysfunction in Quinpirole Sensitization Model of Obsessive-Compulsive Disorder
Brožka, Hana ; Stuchlík, Aleš (advisor) ; Jendelová, Pavla (referee) ; Kelemen, Eduard (referee)
Obsessive-compulsive disorder (OCD) is a serious psychiatric condition manifested by repeated thoughts followed by stereotypic compulsive behavior. Alterations to cortico-thalamo-striato- cortical circuits are most often implicated in the pathophysiology of OCD. However, many studies have also found a changed volume, shape and activity of the hippocampus in OCD patients. This work focused on the activity of hippocampal CA1 cells during stereotypical checking behavior and on cognitive flexibility in a quinpirole (QNP) sensitization model of OCD. The activity of CA1 hippocampal cells during stereotypical checking was assessed in an enriched open-field test in QNP sensitized rats. Arc+ (activity-regulated cytoskeletal associated protein, or Arg 3.1) mRNA expression profiles were determined in CA1 coronal hippocampal sections following stereotypical checking. After the establishment of stereotypical checking (10 sessions), rats were exposed to the arena and sacrificed after 5 minutes. QNP sensitized animals visited the same objects with the same frequency as during previous sessions, while control rats did not. Locomotor activity was comparable between QNP treated rats and controls. Following sacrifice, rat brains were flash frozen and sliced to 20 µm thick sections. Sections, mounted on slides, were hybridized...
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Hippocampus Dysfunction in Quinpirole Sensitization Model of Obsessive-Compulsive Disorder
Brožka, Hana ; Stuchlík, Aleš (advisor) ; Jendelová, Pavla (referee) ; Kelemen, Eduard (referee)
Obsessive-compulsive disorder (OCD) is a serious psychiatric condition manifested by repeated thoughts followed by stereotypic compulsive behavior. Alterations to cortico-thalamo-striato- cortical circuits are most often implicated in the pathophysiology of OCD. However, many studies have also found a changed volume, shape and activity of the hippocampus in OCD patients. This work focused on the activity of hippocampal CA1 cells during stereotypical checking behavior and on cognitive flexibility in a quinpirole (QNP) sensitization model of OCD. The activity of CA1 hippocampal cells during stereotypical checking was assessed in an enriched open-field test in QNP sensitized rats. Arc+ (activity-regulated cytoskeletal associated protein, or Arg 3.1) mRNA expression profiles were determined in CA1 coronal hippocampal sections following stereotypical checking. After the establishment of stereotypical checking (10 sessions), rats were exposed to the arena and sacrificed after 5 minutes. QNP sensitized animals visited the same objects with the same frequency as during previous sessions, while control rats did not. Locomotor activity was comparable between QNP treated rats and controls. Following sacrifice, rat brains were flash frozen and sliced to 20 µm thick sections. Sections, mounted on slides, were hybridized...
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Neuronal activity during stereotypical behavior in quinpirole induced animal model of Obsessive Compulsive Disorder (OCD)
Alexová, Daniela ; Valeš, Karel (advisor) ; Kopřivová, Jana (referee)
The main aim of this study was to determine the changes in neuronal activity of anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and medial prefrontal cortex (MPC) in rats sensitized to D2/D3 receptor agonist quinpirole (QNP) during exploration of enriched open field arena. During the experiment, the evaluation of behavioural changes induced by quinpirole sensitization were also assessed and compared to previous results. For the purpose of this study, twenty-two adult male Long-Evans rats were used. The half of the rats was sensitized to QNP by receiving daily subcutaneous injections of quinpirole (0,5 mg/kg) while the other half received saline. Both groups were habituated for ten days to open-field arena enriched with two metal objects. The behaviour of animals was videotaped and the data about locomotion and the number of visits of each locale was obtained. On the eleventh day, the part of saline and quinpirole treated groups explored the open-field arena (t = 5 min) while the other two subgroups were left as respective cage-controls. Immediately after the end of experiment, all rats were sacrificed, and the extracted brains were cryopreserved. To determine the changes in neuronal activity of selected brain regions, fluorescence in situ hybridization of immediate early gene Arc was...
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Vliv klomipraminu a risperidonu na učení a flexibilitu u animálního modelu obsedantně kompulzivní poruchy
Radostová, Dominika ; Stuchlík, Aleš (advisor) ; Kopřivová, Jana (referee)
Chronic sensitization of dopamine D2/D3 receptors by agonist quinpirole (QNP) induces compulsive checking behaviour in rats, which is considered an animal model of obsessive-compulsive disorder (OCD). Previous study revealed deficit in cognitive flexibility in QNP sensitized rats. This thesis focused on determining if this cognitive flexibility deficit is ameliorated by co-administration of clomipramine (CMI), risperidone (RIS) or combination of both (CMI+RIS) to QNP treatment. Aversively motivated active place avoidance task on a Carousel maze with reversal was used. The number of entrances into a to-be-avoided shock sector was evaluated as measure of performance. Six treatment groups were used: control group, QNP group, CMI group, QNP/CMI combination, QNP/RIS combination and QNP/CMI/RIS combination. Surprisingly, when compared alone, significantly worse acquisition was observed for QNP group compared to control group. However, similarly to previous study, QNP group had a worse performance in a first reversal session compared to control group. When all groups were compared, only QNP/CMI group had worse initial learning compared to control group. In reversal learning, only QNP treated group had a significantly more entrances than control group in first reversal session. Results suggest that co-treatment...
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