Dopamine D receptors (DRs) of the ventral pallidum (VP) play important role in motivational and learning processes, however, their potential role in triggering schizophrenic symptoms has not been investigated, yet. In the present experiments the effects of locally administered DR agonist quinpirole were investigated on behavioral parameters related to sensorimotor gating, motor activity and food-motivated labyrinth learning. Two weeks after bilateral implantation of microcannulae into the VP, the acute (30 min) and delayed (3, 21 and 24 h) effects of quinpirole microinjection (1 μg/0.4 μL at both sides) were investigated in Wistar and schizophrenia model (Wisket substrain) rats in prepulse inhibition (PPI) and the reward-based Ambitus tests. Quinpirole administration did not modify the impaired sensorimotor gating in Wisket rats, but it led to significant deficit in Wistar animals. Regarding the locomotor activity in the Ambitus test, no effects of quinpirole were detected in either groups at the investigated time points. In contrast, quinpirole resulted in decreased exploratory and food-collecting activities in Wistar rats with 21 and 24 h delay. Though, impaired food-related motivation could be observed in Wisket rats, but quinpirole treatment did not result in further deterioration. In summary, our results showed that the VP DR activation in Wistar rats induces symptoms similar to those observed in schizophrenia model Wisket rats. These data suggest that Wisket rats might have significant alterations in the functional activity of VP, which might be due to its enhanced dopaminergic activity.
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http://dx.doi.org/10.1016/j.bbr.2020.113047 | DOI Listing |
Curr Neuropharmacol
July 2023
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine & Institute of Neurosciences, School of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona, 08193, Spain.
Schizophrenia is a chronic and severe mental disorder with high heterogeneity in its symptoms clusters. The effectiveness of drug treatments for the disorder is far from satisfactory. It is widely accepted that research with valid animal models is essential if we aim at understanding its genetic/ neurobiological mechanisms and finding more effective treatments.
View Article and Find Full Text PDFInt J Mol Sci
July 2022
Department of Medical Imaging, Division of Nuclear Medicine and Translational Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Recently, morphological impairments have been detected in the brain of a triple-hit rat schizophrenia model (Wisket), and delayed depressive effects of caffeine treatment in both control and Wisket animals have also been shown. The aims of this study were to determine the basal and caffeine-induced acute (30 min) and delayed (24 h) changes in the cerebral fluorodeoxyglucose (F-FDG) uptake by positron emission tomography (PET) in control and Wisket rats. No significant differences were identified in the basal whole-brain metabolism between the two groups, and the metabolism was not modified acutely by a single intraperitoneal caffeine (20 mg/kg) injection in either group.
View Article and Find Full Text PDFFront Behav Neurosci
January 2022
Department of Physiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Electroencephalography studies in schizophrenia reported impairments in circadian rhythm and oscillatory activity, which may reflect the deficits in cognitive and sensory processing. The current study evaluated the circadian rhythm and the state-dependent oscillatory pattern in control Wistar and a multiple hit schizophrenia rat model (Wisket) using custom-made software for identification of the artifacts and the classification of sleep-wake stages and the active and quiet awake substages. The Wisket animals have a clear light-dark cycle similar to controls, and their sleep-wake rhythm showed only a tendency to spend more time in non-rapid eye movement (NREM) and less in rapid eye movement (REM) stages.
View Article and Find Full Text PDFPhysiol Behav
February 2022
Department of Physiology, Albert Szent-Györgyi Medical School, University of Szeged, Dóm tér 10., Szeged, H-6720, Hungary.
It is well-known that the poor cognition in schizophrenia is strongly linked to negative symptoms, including motivational deficit, which due to, at least partially, anhedonia. The goal of this study was to explore whether the schizophrenia-like Wisket animals with impaired motivation (obtained in the reward-based hole-board test), also show decreased hedonic behavior (investigated with the sucrose preference test). While neurochemical alterations of different neurotransmitter systems have been detected in the Wisket rats, no research has been performed on structural changes.
View Article and Find Full Text PDFSci Rep
August 2021
Institute of Biochemistry, ELKH Biological Research Center, 6726, Szeged, Hungary.
The low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies.
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