Effort-based decision-making is particularly relevant to psychiatric conditions where motivation deficits are prominent features. Despite its clinical significance, the neurochemical mechanisms of this cognitive process remain unclarified. This study explores the impact of serotonin synthesis inhibition (PCPA) and modulation of serotonin release and 5-HT1A receptor agonism (8-OH-DPAT) on effort-based decision-making in rats. Adult male rats were trained in a modified T-maze task where they could obtain a high reward for climbing a mesh barrier or a low reward for no extra effort. Following training, rats received either acute 8-OH-DPAT treatment or subchronic PCPA treatment and were tested on their choices between high- and low-effort arms. The goal-arm choices and goal-arm entrance latencies were recorded. Next, homovanillic acid and 5-hydroxyindoleacetic acid, metabolites of dopamine and serotonin, respectively, were quantified in the rats' prefrontal cortex, striatum, and hippocampus. 8-OH-DPAT significantly increased low-effort, low-reward choices and increased goal-arm latency. In contrast, PCPA treatment did not affect these measures. Both PCPA and 8-OH-DPAT significantly decreased 5-hydroxyindoleacetic acid levels in the prefrontal cortex and the hippocampus. 8-OH-DPAT treatment was also associated with decreased homovanillic acid levels in the hippocampus. Our findings suggest that the overall reduction of serotonin levels alone does not affect effort-based decision-making and highlights the possible role of the hippocampus and the 5-HT1A receptor in this cognitive process.

• MeSH
• 8-hydroxy-2-(di-N-propylamino)tetralin * farmakologie   MeSH
• agonisté serotoninového receptoru 5-HT1 farmakologie   MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• chování zvířat účinky léků   MeSH
• krysa rodu Rattus MeSH
• odměna MeSH
• potkani Sprague-Dawley MeSH
• rozhodování * fyziologie   účinky léků   MeSH
• serotonin * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 8-hydroxy-2-(di-N-propylamino)tetralin * MeSH
• agonisté serotoninového receptoru 5-HT1 MeSH
• serotonin * MeSH

Clinical diagnosis of Parkinson's disease (PD) occurs typically when a substantial proportion of dopaminergic neurons in the substantia nigra (SN) already died, and the first motor symptoms appear. Therefore, tools enabling the early diagnosis of PD are essential to identify early-stage PD patients in which neuroprotective treatments could have a significant impact. Here, we test the utility and sensitivity of the diffusion kurtosis imaging (DKI) in detecting progressive microstructural changes in several brain regions of mice exposed to chronic intragastric administration of rotenone, a mouse model that mimics the spatiotemporal progression of PD-like pathology from the ENS to the SN as described by Braak's staging. Our results show that DKI, especially kurtosis, can detect the progression of pathology-associated changes throughout the CNS. Increases in mean kurtosis were first observed in the dorsal motor nucleus of the vagus (DMV) after 2 months of exposure to rotenone and before the loss of dopaminergic neurons in the SN occurred. Remarkably, we also show that limited exposure to rotenone for 2 months is enough to trigger the progression of the disease in the absence of the environmental toxin, thus suggesting that once the first pathological changes in one region appear, they can self-perpetuate and progress within the CNS. Overall, our results show that DKI can be a useful radiological marker for the early detection and monitoring of PD pathology progression in patients with the potential to improve the clinical diagnosis and the development of neuroprotective treatments.

• Klíčová slova
• MRI, Parkinson, alpha synuclein, diffusion kurtosis imaging, rotenone, s disease, tract-based spatial statistics,
• MeSH
• aplikace orální MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• časové faktory MeSH
• dopaminergní neurony účinky léků   patologie   MeSH
• insekticidy toxicita   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• parkinsonské poruchy chemicky indukované   diagnostické zobrazování   patologie   MeSH
• progrese nemoci * MeSH
• rotenon aplikace a dávkování   toxicita   MeSH
• zobrazování difuzních tenzorů metody   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• insekticidy MeSH
• rotenon MeSH

Anxiety-related behaviors in mice are often assessed over short periods starting immediately after introducing the animals in a dedicated apparatus. In these usual conditions (5-10 min periods), the cerebellar Lurcher mutants showed disinhibited behaviors characterized by abnormally high exploration of the aversive areas in the elevated plus-maze test. We nevertheless observed that this disinhibition sharply weakened after 10 min. We therefore decided to further investigate the influence of the disinhibition on the intrinsic and anxiety-related exploratory behaviors in Lurcher mice, with a special focus on familiarization effects. To this end, we used an innovative apparatus, the Dual Maze, permitting to tune the familiarization level of animals to the experimental context before they are faced with more (open configuration of the device) or less (closed configuration of the device) aversive areas. Chlordiazepoxide administration in BALB/c mice in a preliminary experiment confirmed both the face and the predictive validity of our device as anxiety test and its ability to measure exploratory motivation. The results obtained with the Lurcher mice in the open configuration revealed that 20 min of familiarization to the experimental context abolished the behavioral abnormalities they exhibited when not familiarized with it. In addition, their exploratory motivation, as measured in the closed configuration, was comparable to that of their non-mutant littermates, whatever the level of familiarization applied. Exemplifying the interest of this innovative device, the results we obtained in the Lurcher mutants permitted to differentiate between the roles played by the cerebellum in exploratory motivation and stress-related behaviors.

• Klíčová slova
• Anxiety, Behavioral test, Cerebellum, Exploratory behavior, Lurcher mutant, Stress,
• MeSH
• bludiště - učení fyziologie   MeSH
• chování zvířat fyziologie   MeSH
• inhibice (psychologie) * MeSH
• motivace fyziologie   MeSH
• mozeček MeSH
• myši - mutanty neurologické MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• neuropsychologické testy * MeSH
• pátrací chování fyziologie   MeSH
• rozpoznávání (psychologie) fyziologie   MeSH
• úzkost patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Lurcher mutant mice of the C3H strain provide a model of both cerebellar and retinal degeneration. Therefore, they enable the study of the behavior of cerebellar mutants under disabled visual orientation conditions. We aimed to examine cerebellar Lurcher mutants and wild type mice with intact cerebella with and without retinal degeneration employing the rotarod and Morris water maze tests. The positions of the hidden platform and the starting point in the water maze test were stable so as to enable the use of both idiothetic navigation and visual inputs. The Lurcher mice evinced approximately 90 % shorter fall latencies on the rotarod than did the wild type mice. Retinal degeneration exerted no impact on motor performance. Only the wild type mice with normal retina were able to find the water maze platform efficiently. The wild type mice with retinal degeneration developed immobility (almost 25 % of the time) as a sign of behavioral despair. The Lurchers maintained high swimming activity as a potential manifestation of stress-induced behavioral disinhibition and their spatial performance was related to motor skills and swim speed. We demonstrated that both motor deficit and pathological behavior have the potential to contribute to abnormal performance in spatial tasks. Thus, spatial disability in cerebellar mutants is most likely a complex consequence of multiple disturbances related to cerebellar dysfunction.

• Klíčová slova
• Behavioral control, Cerebellum, Idiothetic navigation, Lurcher mouse,
• MeSH
• bludiště - učení fyziologie   MeSH
• degenerace retiny genetika   patologie   MeSH
• motorické dovednosti fyziologie   MeSH
• mozeček patologie   MeSH
• myši - mutanty neurologické MeSH
• myši inbrední C3H MeSH
• myši MeSH
• neurodegenerativní nemoci genetika   patologie   MeSH
• slepota genetika   patologie   MeSH
• vnímání prostoru fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Epilepsy, the most common neurologic disorder in childhood, is associated with a subset of psychiatric dysfunctions, including cognitive deficits, and alterations in emotionality (e.g., anxiety and depression) and social functioning. In the present study, we evaluated an integrative set of behavioral responses, including cognitive/socio-cognitive and emotional dimensions, using a number of behavioral paradigms in the LiCl/pilocarpine model of status epilepticus (SE) in rats. The aims of the study were to examine whether SE affects: 1) non-associative learning (habituation of exploratory behavior); 2) investigatory response to an indifferent stimulus object; 3) sociability/social novelty preference; 4) social recognition or discrimination; and 4) short- and long-term memory in the Morris water maze (MWM). Finally, we investigated the morphology of key brain structures involved in the examined behavioral dysfunctions. SE did not affect habituation to an open-field arena in juvenile (P25), adolescent (P32), or adult (P80) rats. SE rats spent less time in the central part of the arena. SE adolescent rats (P32) displayed a higher number of rearings with a shorter duration. SE rats displayed a markedly attenuated investigatory response to an indifferent stimulus object. SE rats in all age groups demonstrated pronounced deficits in sociability and the preference for social novelty. In addition, SE rats spent a reduced amount of time investigating a juvenile rat upon first exposure. After 30 min re-exposure together with an additional, novel juvenile, the SE rats spent equal time investigating both juveniles. In the MWM task, acquisition was unimpaired but there was a deficit in delayed memory retention after 10 days. SE did not affect cognitive flexibility expressed by reversal learning. Together, these findings suggest that early-life SE leads to alterations in emotional/anxiety-related behavior and affects sociability/preference for social novelty and social discrimination. Early-life SE did not alter acquisition of spatial learning, but it impaired delayed retention. Using Fluoro Jade B staining performed 24 h after SE revealed apparent neurodegeneration in the dorsal hippocampus, mediodorsal thalamic nucleus and medial amygdala, brain areas that are critically involved in network underlying emotional behavior and cognitive functions.

• Klíčová slova
• Anxiety, Cognition, Depression, Epilepsy, Exploratory behavior, Hippocampus, Pilocarpine, Rats, Spatial learning, Status epilepticus,
• MeSH
• bludiště - učení fyziologie   MeSH
• chování zvířat fyziologie   MeSH
• epilepsie temporálního laloku patologie   patofyziologie   MeSH
• kognitivní poruchy patologie   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• mozek patologie   patofyziologie   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

Prenatal exposure to caffeine can cause developmental problems. This study determined chronic influence of prenatal caffeine at relatively higher doses on cognitive functions in the rat offspring. Pregnant Sprague-Dawley rats (4-month-old) were exposed to caffeine (20 mg/kg, twice a day) for whole pregnancy from gestational day 4. Fetal and offspring body and brain weight was measured. Learning and memory were tested in adult offspring with Morris water maze. Learning and memory-related receptors were measured. The exposure to prenatal caffeine not only caused fetal growth restriction, but also showed long-term effects on learning and memory in the offspring. The caffeine offspring exhibited longer escape latency and path length in navigation testing. The number of passing the target was significantly reduced in those offspring. The expression of adenosine A(1) and A(2A) receptors, nuclear PKA C(alpha), C(beta) subunits, and pCREB were significantly increased in the fetal and neonatal brain, and suppressed in the hippocampus of the adult offspring. The expression of BDNF and TrkB were reduced regardless of various ages. The results suggest that intrauterine programming dysfunction of adenosine receptors and the down-stream of cAMP/PKA/pCREB system may play an important role in prenatal caffeine induced cognition disorders in the adult offspring.

• MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• kofein toxicita   MeSH
• krysa rodu Rattus MeSH
• mozkový neurotrofický faktor metabolismus   MeSH
• paměť účinky léků   fyziologie   MeSH
• poruchy paměti chemicky indukované   diagnóza   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• protein vázající cAMP responzivní element metabolismus   MeSH
• proteinkinasy závislé na cyklickém AMP metabolismus   MeSH
• purinergní receptory P1 metabolismus   MeSH
• signální transdukce účinky léků   fyziologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   diagnóza   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Bdnf protein, rat MeSH Prohlížeč
• Creb1 protein, rat MeSH Prohlížeč
• kofein MeSH
• mozkový neurotrofický faktor MeSH
• protein vázající cAMP responzivní element MeSH
• proteinkinasy závislé na cyklickém AMP MeSH
• purinergní receptory P1 MeSH

The present study evaluates the protective role of Quercetin (Quer), against immobilization stress- induced anxiety, depression and cognition alteration in mice using behavioral and biochemical parameters. 24 adult Albino mice were distributed into 2 groups vehicle (n=12; 1 ml/kg) and Quer injected (n=12; 20 mg/kg/ml). The animals received their respective treatment for 14 days. On day 15, after the drug administration, animals were sub-divided into 4 groups (n=6); (i) unstressed + vehicle; (ii) stressed + vehicle; (iii) unstressed + Quer; (iv) stressed + Quer. On day 16, 24 h after the immobilization stress behavioral activities (light-dark activity, elevated plus maze, Morris water maze, and forced swim test) monitored and then animals were decapitated 1 h after the drug administration. Brain samples were collected for biochemical (antioxidant enzymes, AChE, ACh, 5-HT and its metabolite) analysis. The present study indicates the Quer reversed the stress-induced anxiety and depression, in addition, memory performance was more enhanced in stressed group. Following the treatment of Quer, stress-induced elevation of lipid peroxidation and suppression of antioxidant enzymes were also reversed. Administration of Quer decreased AChE in unstressed, while levels of acetylcholine were increased in vehicle and Quer treated stressed animals. The metabolism of 5-HT was increased in Quer treated stressed than unstressed animals. In conclusion, the present finding showed that Quer could prevent the impairment of antioxidant enzymes and also regulate the serotonergic and cholinergic neurotransmission and produce antianxiety, antidepressant effect and enhance memory following 2 h immobilization stress in mice.

• MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• deprese metabolismus   prevence a kontrola   psychologie   MeSH
• myši MeSH
• paměť účinky léků   fyziologie   MeSH
• psychický stres farmakoterapie   metabolismus   psychologie   MeSH
• quercetin farmakologie   terapeutické užití   MeSH
• úzkost metabolismus   prevence a kontrola   psychologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• quercetin MeSH

Obesity and type 2 diabetes mellitus (T2DM) were characterized as risk factors for Alzheimer's disease (AD) development. Subsequently, T2DM drugs, such as liraglutide, were proven to be neuroprotective compounds attenuating levels of amyloid deposits, and tau hyperphosphorylation, both hallmarks of AD. The central anorexigenic effects of liraglutide inspired us to examine the potential neuroprotective effects of palm11-PrRP31, a strong anorexigenic analog with glucose-lowering properties, in THY-Tau22 mice overexpressing mutated human tau, a model of AD-like tau pathology. Seven-month-old THY-Tau22 mice were subcutaneously infused with palm11-PrRP31 for 2 months. Spatial memory was tested before and after the treatment, using a Y-maze. At the end of the treatment, mice were sacrificed by decapitation and hippocampi were dissected and analyzed by immunoblotting with specific antibodies. Treatment with palm11-PrRP31 resulted in significantly improved spatial memory. In the hippocampi of palm11-PrRP31-treated THY-Tau22 mice, tau protein phosphorylation was attenuated at Thr231, Ser396, and Ser404, the epitopes linked to AD progression. The mechanism of this attenuation remains unclear, since the activation of those kinases most implicated in tau hyperphosphorylation, such as GSK-3β, JNK, or MAPK/ERK1/2, remained unchanged by palm11-PrRP31 treatment. Furthermore, we observed a significant increase in the amount of postsynaptic density protein PSD95, and a non-significant increase of synaptophysin, both markers of increased synaptic plasticity, which could also result in improved spatial memory of THY-Tau22 mice treated with palm11-PrRP31. Palm11-PrRP31 seems to be a potential tool for the attenuation of neurodegenerative disorders in the brain. However, the exact mechanism of its action must be elucidated.

• Klíčová slova
• Alzheimer’s disease, THY-Tau22 mice, palm11-PrRP31, spatial memory, synaptic plasticity, tau hyperphosphorylation,
• MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• fosforylace účinky léků   MeSH
• hipokampus účinky léků   metabolismus   patologie   MeSH
• hormon uvolňující prolaktin analogy a deriváty   farmakologie   terapeutické užití   MeSH
• krátkodobá paměť účinky léků   fyziologie   MeSH
• modely nemocí na zvířatech MeSH
• myši transgenní MeSH
• neuroprotektivní látky farmakologie   MeSH
• poruchy paměti farmakoterapie   metabolismus   patologie   MeSH
• prostorová paměť účinky léků   fyziologie   MeSH
• proteiny tau metabolismus   MeSH
• tauopatie farmakoterapie   metabolismus   patologie   psychologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hormon uvolňující prolaktin MeSH
• Mapt protein, mouse MeSH Prohlížeč
• neuroprotektivní látky MeSH
• palm11-PrRP31 MeSH Prohlížeč
• proteiny tau MeSH

Baclofen is the only clinically available metabotropic GABA(B) receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases.

• MeSH
• agonisté receptorů GABA-B aplikace a dávkování   MeSH
• baklofen aplikace a dávkování   MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• paměť účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• prostorové učení účinky léků   fyziologie   MeSH
• rozvrh dávkování léků MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agonisté receptorů GABA-B MeSH
• baklofen MeSH

BACKGROUND: High plasma homocysteine (Hcy) level is related to higher risk of Alzheimer's disease (AD) and lower cognitive performance in older adults. OBJECTIVE: To assess the association between plasma Hcy level and real-space navigation performance and the role of vascular risk and protective factors, APOE status, and white matter lesions (WML) on this association. METHODS: Ninety-two non-demented older adults (29 with amnestic mild cognitive impairment, 46 with subjective cognitive decline, and 17 cognitively normal older adults) underwent spatial navigation testing of egocentric, allocentric, and mixed navigation in a real-space analogue of the Morris water maze, neuropsychological examination, blood collection, and MRI brain scan with evaluation of WML. RESULTS: In the regression analyses controlling for age, gender, education, and depressive symptoms, higher plasma Hcy level was related to worse mixed and egocentric (β= 0.31; p = 0.003 and β= 0.23; p = 0.017) but not allocentric (p > 0.05) navigation performance. Additional controlling for vascular risk and protective factors, WML, and APOE status did not modify the results. High total cholesterol and low vitamin B12 and folate levels increased the adverse effect of Hcy on egocentric and mixed navigation. WML did not explain the association between plasma Hcy level and navigation performance. CONCLUSION: Elevated plasma Hcy level may affect real-space navigation performance above and beyond vascular brain changes. This association may be magnified in the presence of high total cholesterol and low folate or vitamin B12 levels. Attention to the level of plasma Hcy may be a viable intervention strategy to prevent decline in spatial navigation in non-demented older adults.

• Klíčová slova
• APOE, Alzheimer’s disease, homocysteine, mild cognitive impairment, spatial navigation, subjective cognitive decline, vascular factors,
• MeSH
• bludiště - učení fyziologie   MeSH
• diskriminace (psychologie) MeSH
• homocystein krev   MeSH
• kognitivní dysfunkce krev   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• prostorová navigace fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sluchová percepce fyziologie   MeSH
• stárnutí krev   fyziologie   MeSH
• studie případů a kontrol MeSH
• záznam o duševním stavu MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• homocystein MeSH