Methylphenidate is a stimulant used to treat attention deficit and hyperactivity disorder (ADHD). In the last decade, illicit use of methylphenidate has increased among healthy young adults, who consume the drug under the assumption that it will improve cognitive performance. However, the studies that aimed to assess the methylphenidate effects on memory are not consistent. Here, we tested whether the effect of methylphenidate on a spatial memory task can be explained as a motivational and/or a reward effect. We tested the effects of acute and chronic i.p. administration of 0.3, 1 or 3 mg/kg of methylphenidate on motivation, learning and memory by using the 8-arm radial maze task. Adult male Wistar rats learned that 3 of the 8 arms of the maze were consistently baited with 1, 3, or 6 sucrose pellets, and the number of entries and reentries into reinforced and non-reinforced arms of the maze were scored. Neither acute nor chronic (20 days) methylphenidate treatment affected the number of entries in the non-baited arms. However, chronic, but not acute, 1-3 mg/kg methylphenidate increased the number of reentries in the higher reward arms, which suggests a motivational/rewarding effect rather than a working memory deficit. In agreement with this hypothesis, the methylphenidate treatment also decreased the approach latency to the higher reward arms, increased the approach latency to the low reward arm, and increased the time spent in the high, but not low, reward arm. These findings suggest that methylphenidate may act more as a motivational enhancer rather than a cognitive enhancer in healthy people.
- MeSH
- hyperkinetická porucha * farmakoterapie MeSH
- krysa rodu rattus MeSH
- methylfenidát * farmakologie terapeutické užití MeSH
- motivace MeSH
- odměna MeSH
- potkani Wistar MeSH
- stimulanty centrálního nervového systému * farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The nucleus accumbens (NAc) is considered an interface between motivation and action, with NAc neurons playing an important role in promoting reward approach. However, the encoding by NAc neurons that contributes to this role remains unknown. We recorded 62 NAc neurons in male Wistar rats (n = 5) running towards rewarded locations in an 8-arm radial maze. Variables related to locomotor approach kinematics were the best predictors of the firing rate for most NAc neurons. Nearly 18% of the recorded neurons were inhibited during the entire approach run (locomotion-off cells), suggesting that reduction in firing of these neurons promotes initiation of locomotor approach. 27% of the neurons presented a peak of activity during acceleration followed by a valley during deceleration (acceleration-on cells). Together, these neurons accounted for most of the speed and acceleration encoding identified in our analysis. In contrast, a further 16% of neurons presented a valley during acceleration followed by a peak just prior to or after reaching reward (deceleration-on cells). These findings suggest that these three classes of NAc neurons influence the time course of speed changes during locomotor approach to reward.
- MeSH
- biomechanika MeSH
- krysa rodu rattus MeSH
- lokomoce MeSH
- neurony * fyziologie MeSH
- nucleus accumbens * fyziologie MeSH
- odměna MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Finding a cure for Alzheimer's disease (AD) has been notoriously challenging for many decades. Therefore, the current focus is mainly on prevention, timely intervention, and slowing the progression in the earliest stages. A better understanding of underlying mechanisms at the beginning of the disease could aid in early diagnosis and intervention, including alleviating symptoms or slowing down the disease progression. Changes in social cognition and progressive parvalbumin (PV) interneuron dysfunction are among the earliest observable effects of AD. Various AD rodent models mimic these early alterations, but only a narrow field of study has considered their mutual relationship. In this review, we discuss current knowledge about PV interneuron dysfunction in AD and emphasize their importance in social cognition and memory. Next, we propose oxytocin (OT) as a potent modulator of PV interneurons and as a promising treatment for managing some of the early symptoms. We further discuss the supporting evidence on its beneficial effects on AD-related pathology. Clinical trials have employed the use of OT in various neuropsychiatric diseases with promising results, but little is known about its prospective impacts on AD. On the other hand, the modulatory effects of OT in specific structures and local circuits need to be clarified in future studies. This review highlights the connection between PV interneurons and social cognition impairment in the early stages of AD and considers OT as a promising therapeutic agent for addressing these early deficits.
- MeSH
- Alzheimerova nemoc * patologie MeSH
- hipokampus patologie MeSH
- interneurony MeSH
- kognice MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši transgenní MeSH
- oxytocin MeSH
- parvalbuminy metabolismus MeSH
- prospektivní studie MeSH
- sociální kognice MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The role of rodent hippocampus has been intensively studied in different cognitive tasks. However, its role in discrimination of objects remains controversial due to conflicting findings. We tested whether the number and type of features available for the identification of objects might affect the strategy (hippocampal-independent vs. hippocampal-dependent) that rats adopt to solve object discrimination tasks. We trained rats to discriminate 2D visual objects presented on a computer screen. The objects were defined either by their shape only or by multiple-features (a combination of filling pattern and brightness in addition to the shape). Our data showed that objects displayed as simple geometric shapes are not discriminated by trained rats after their hippocampi had been bilaterally inactivated by the GABAA-agonist muscimol. On the other hand, objects containing a specific combination of non-geometric features in addition to the shape are discriminated even without the hippocampus. Our results suggest that the involvement of the hippocampus in visual object discrimination depends on the abundance of object's features.
- MeSH
- agonisté receptorů GABA-A farmakologie MeSH
- chování zvířat účinky léků fyziologie MeSH
- diskriminační učení účinky léků fyziologie MeSH
- generalizace (psychologie) účinky léků fyziologie MeSH
- hipokampus účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- muscimol farmakologie MeSH
- operantní podmiňování účinky léků fyziologie MeSH
- potkani Long-Evans MeSH
- rozpoznávání obrazu účinky léků fyziologie MeSH
- vnímání tvaru účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
OBJECTIVES: Deficit in visuospatial functions can influence both simple and complex daily life activities. Despite the fact that visuospatial deficit was reported in schizophrenia, research on visuospatial functions as an independent entity is limited. Our study aims to elucidate the impact of visuospatial deficit in comparison with verbal deficit on global functioning and quality of life in the first psychotic episode of schizophrenia spectrum disorder (FES). The significance of clinical symptoms and antipsychotic medication was also studied. METHODS: Thirty-six FES patients and a matched group of healthy controls (HC group) were assessed with a neuropsychological battery focused on visuospatial (VIS) and verbal (VERB) functions. Using multiple regression analysis, we evaluated the cumulative effect of VERB and VIS functions, psychiatric symptoms (PANSS) and antipsychotic medication on global functioning (GAF) and quality of life (WHOQOL-BREF) in the FES group. RESULTS: The FES group demonstrated significant impairment both in VIS and VERB cognitive abilities compared to the HC group. Antipsychotic medication did not significantly affect either VIS or VERB functioning. PANSS was not related to cognitive functioning, apart from the Trail Making Test B. In the FES group, the GAF score was significantly affected by the severity of positive symptoms and VERB functioning, explaining together 60% of GAF variability. The severity of negative and positive symptoms affected only the Physical health domain of WHOQOL-BREF. The degree of VERB deficit was associated with both Physical and Psychological health. Although we did not find any relation between VIS functioning, GAF, and WHOQOL-BREF, a paradoxical finding emerged in the Environment quality domain, where a worse quality of the environment was associated with better VIS functioning. CONCLUSIONS: Our results suggest that the deficit in VIS functions is an integral part of cognitive deficit in schizophrenia spectrum disorders, rather than a side effect of symptomatology or antipsychotic medication. Moreover, VERB functioning was a better predictor of GAF and WHOQOL-BREF than VIS functioning. Given the findings of negative or missing effect of VIS deficit on WHOQOL-BREF and GAF, the accuracy of these measures in evaluating the impact of global cognitive deficit on everyday life in schizophrenia could be questioned.
- Publikační typ
- časopisecké články MeSH
Objectives: Cognitive deficit is considered to be a characteristic feature of schizophrenia disorder. A similar cognitive dysfunction was demonstrated in animal models of schizophrenia. However, the poor comparability of methods used to assess cognition in animals and humans could be responsible for low predictive validity of current animal models. In order to assess spatial abilities in schizophrenia and compare our results with the data obtained in animal models, we designed a virtual analog of the Morris water maze (MWM), the virtual Four Goals Navigation (vFGN) task. Methods: Twenty-nine patients after the first psychotic episode with schizophrenia symptoms and a matched group of healthy volunteers performed the vFGN task. They were required to find and remember four hidden goal positions in an enclosed virtual arena. The task consisted of two parts. The Reference memory (RM) session with a stable goal position was designed to test spatial learning. The Delayed-matching-to-place (DMP) session presented a modified working memory protocol designed to test the ability to remember a sequence of three hidden goal positions. Results: Data obtained in the RM session show impaired spatial learning in schizophrenia patients compared to the healthy controls in pointing and navigation accuracy. The DMP session showed impaired spatial memory in schizophrenia during the recall of spatial sequence and a similar deficit in spatial bias in the probe trials. The pointing accuracy and the quadrant preference showed higher sensitivity toward the cognitive deficit than the navigation accuracy. Direct navigation to the goal was affected by sex and age of the tested subjects. The age affected spatial performance only in healthy controls. Conclusions: Despite some limitations of the study, our results correspond well with the previous studies in animal models of schizophrenia and support the decline of spatial cognition in schizophrenia, indicating the usefulness of the vFGN task in comparative research.
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- kognitivní poruchy diagnóza MeSH
- lidé MeSH
- schizofrenie diagnóza MeSH
- uživatelské rozhraní počítače * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Rat hippocampus plays a crucial role in many spatial tasks, including recognition of position of objects, which can be approached and explored. Whether hippocampus is also necessary for recognizing positions of objects located in an inaccessible part of the environment remains unclear. To address this question, we conditioned rats to press a lever when an object displayed on a distant computer screen was in a particular position ("reward position") and not to press the lever when the object was in other positions ("nonreward positions"). After the rats had reached an asymptotic performance, the role of the dorsal hippocampus was assessed by blocking its activity with muscimol. The rats without functional dorsal hippocampus did not discriminate the reward position from the nonreward positions. Then the same rats were trained to discriminate light and dark conditions. The hippocampal inactivation did not disrupt the ability to discriminate these two conditions. It indicated that the inactivation itself had no major effect on the operant behavior and its control by visual stimuli. We conclude that rats use dorsal hippocampus for recognizing positions of objects located in an inaccessible part of the environment.
- MeSH
- antagonisté receptorů GABA-A farmakologie MeSH
- chování zvířat fyziologie MeSH
- diskriminace (psychologie) účinky léků fyziologie MeSH
- hipokampus účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- muscimol farmakologie MeSH
- operantní podmiňování MeSH
- potkani Long-Evans MeSH
- rozpoznávání (psychologie) účinky léků fyziologie MeSH
- vnímání prostoru účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
