Neural components enabling flexible cognition and behavior are well-established, and depend mostly on proper intercommunication within the prefrontal cortex (PFC) and striatum. However, dense projections from the ventral hippocampus (vHPC) alter the functioning of the medial PFC (mPFC). Dysfunctional hippocampo-prefrontal connectivity negatively affects the integrity of flexible cognition, especially in patients with schizophrenia. In this study, we aimed to test the role of the vHPC and mPFC in a place avoidance task on a rotating arena using two spatial flexibility task variants - reversal learning and set-shifting. To achieve this, we inactivated each of these structures in adult male Long-Evans rats by performing bilateral local muscimol (a GABAA receptor agonist) injections. A significantly disrupted performance was observed in reversal learning in the vHPC-inactivated, but not in the mPFC-inactivated rats. These results confirm the notion that the vHPC participates in some forms of behavioral flexibility, especially when spatial cues are needed. It seems, rather unexpectedly, that the mPFC is not taxed in these flexibility tasks on a rotating arena.

• Klíčová slova
• Behavioral flexibility, Carousel, Muscimol, Prefrontal cortex, Rotating arena, Ventral hippocampus,
• MeSH
• agonisté receptorů GABA-A farmakologie   MeSH
• hipokampus účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• muscimol farmakologie   MeSH
• pozornost účinky léků   fyziologie   MeSH
• prefrontální mozková kůra účinky léků   fyziologie   MeSH
• prostorové vidění účinky léků   fyziologie   MeSH
• reverzní učení účinky léků   fyziologie   MeSH
• učení vyhýbat se 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
• Názvy látek
• agonisté receptorů GABA-A MeSH
• muscimol MeSH

Our previous studies showed that the nootropic drug Cerebrolysin, applied immediately after the traumatic or excitotoxic brain lesion influenced spatial learning and memory. Long-lasting ameliorative effect of Cerebrolysin was found after its 4-week-administration, while two-week-treatment had only temporal effect. With the aim to verify the capability of Cerebrolysin to restore chronically deteriorated learning and memory. The drug was applied 4 months after lesioning the rat's CNS. The present study shows that Cerebrolysin restored learning capability of the lesioned rats. Although their spatial memory was improved in comparison to lesion untreated controls, it did not reach the level of intact controls. The effect was more pronounced after the application of 1.25 ml/kg b. w. of Cerebrolysin than after the application of 2.5 ml/kg b. w.

• MeSH
• aminokyseliny terapeutické užití   MeSH
• chování zvířat účinky léků   MeSH
• krysa rodu Rattus MeSH
• nootropní látky terapeutické užití   MeSH
• poranění mozku komplikace   patologie   psychologie   MeSH
• poruchy paměti farmakoterapie   etiologie   MeSH
• poruchy učení farmakoterapie   etiologie   MeSH
• potkani Long-Evans MeSH
• vnímání prostoru účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• cerebrolysin MeSH Prohlížeč
• nootropní látky MeSH

Adult neurogenesis in the dentate gyrus adds a substantial number of new functional neurons to the hippocampus network in rodents. To date, however, the function of these new granule cells remains unclear. We conducted an experiment to assess the contribution of adult neurogenesis in the dentate gyrus to acquisition and reversal learning in a task that predominantly requires generalization of a rule. Young adult male Long-Evans rats were repeatedly administered either a cytostatic temozolomide or saline for a period of four weeks (3 injections per week). Post treatment, animals were injected with bromodeoxyuridine to quantify adult neurogenesis in the dentate gyrus. For behavioral assessment we used hippocampus-dependent active place avoidance with reversal in a Carousel maze. Animals first learned to avoid a 60° sector on the rotating arena. Afterwards, sector was relocated to the opposite side of the rotating arena (reversal). The administration of temozolomide significantly improved the reversal performance compared to saline-treated rats. Our results suggest a significant, level-dependent, improvement of reversal learning in animals with reduced adult neurogenesis in hippocampus.

• Klíčová slova
• Active avoidance, Adult neurogenesis, Discrimination, Generalization, Hippocampus, Reversal,
• MeSH
• alkylační protinádorové látky farmakologie   MeSH
• dakarbazin analogy a deriváty   farmakologie   MeSH
• gyrus dentatus účinky léků   MeSH
• krysa rodu Rattus MeSH
• neurogeneze účinky léků   MeSH
• neurony účinky léků   MeSH
• potkani Long-Evans MeSH
• prostorové učení účinky léků   MeSH
• reverzní učení účinky léků   MeSH
• temozolomid MeSH
• učení vyhýbat se účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• dakarbazin MeSH
• temozolomid MeSH

In the present study we investigated the sex differences in the effect of adult long-term drug treatment on cognitive functions of Wistar rats, which were prenatally exposed to MA (5mg/kg) or saline. Cognitive functions were tested as an ability of spatial learning in the Morris Water Maze (MWM), which consisted of three types of tests: "Place Navigation Test"; "Probe Test", and "Memory Recall Test". Adult animals were injected daily, after completion of the last trial, either with saline or cocaine (COC; 5mg/kg), MDMA (3,4-methylenedioxy-methamphetamine; 5mg/kg), morphine (MOR; 5mg/kg), or delta-9-tetrahydrocannabinol (THC; 2mg/kg). Results revealed worsened MWM performance in female rats after drug treatment in adulthood. Not only were traditionally investigated parameters affected by drug treatment (latency of platform acquisition, search strategy, distance traveled), but also strategies used by animals (thigmotaxis, scanning). Analyses of search strategies observed in the Place Navigation Test, as well as in the Memory Recall Test, demonstrated variations in the percentage of time spent in thigmotaxis and scanning in females after treatment with COC, MDMA, MOR, and THC. Although we did not see a sensitizing effect of prenatal MA, in some cases the effect of drug treatment in adulthood differed depending on the prenatal drug exposure. The data presented in this study demonstrates that exposure to drugs with various mechanisms of action alters spatial abilities of female rats in the MWM. Alterations in the effect of adult drug treatment with reference to prenatal drug exposure were also found in the present study.

• Klíčová slova
• Long-term drug treatment, Methamphetamine, Morris Water Maze, Sex differences, Spatial learning,
• MeSH
• kognice účinky léků   MeSH
• kokain farmakologie   MeSH
• methamfetamin toxicita   MeSH
• morfin farmakologie   MeSH
• N-methyl-3,4-methylendioxyamfetamin farmakologie   MeSH
• náhodné rozdělení MeSH
• pohlavní dimorfismus * MeSH
• potkani Wistar MeSH
• prostorová navigace účinky léků   MeSH
• prostorové učení účinky léků   MeSH
• psychologické testy MeSH
• psychotropní léky farmakologie   MeSH
• těhotenství MeSH
• tetrahydrokanabinol farmakologie   MeSH
• zpožděný efekt prenatální expozice psychologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kokain MeSH
• methamfetamin MeSH
• morfin MeSH
• N-methyl-3,4-methylendioxyamfetamin MeSH
• psychotropní léky MeSH
• tetrahydrokanabinol MeSH

Age-related hearing loss is linked to cognitive impairment, but the mechanisms that relate to these conditions remain unclear. Evidence shows that the activation of medial olivocochlear (MOC) neurons delays cochlear aging and hearing loss. Consequently, the loss of MOC function may be related to cognitive impairment. The α9/α10 nicotinic receptor is the main target of cholinergic synapses between the MOC neurons and cochlear outer hair cells. Here, we explored spatial learning and memory performance in middle-aged wild-type (WT) and α9-nAChR subunit knock-out (KO) mice using the Barnes maze and measured auditory brainstem response (ABR) thresholds and the number of cochlear hair cells as a proxy of cochlear aging. Our results show non-significant spatial learning differences between WT and KO mice, but KO mice had a trend of increased latency to enter the escape box and freezing time. To test a possible reactivity to the escape box, we evaluated the novelty-induced behavior using an open field and found a tendency towards more freezing time in KO mice. There were no differences in memory, ABR threshold, or the number of cochlear hair cells. We suggest that the lack of α9-nAChR subunit alters novelty-induced behavior, but not spatial learning in middle-aged mice, by a non-cochlear mechanism.

• Klíčová slova
• auditory efferent, cognitive impairment, nicotinic receptor, novel object exploration, spatial learning,
• Publikační typ
• časopisecké články 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

Spatial learning is a widely studied type of animal behavior often considered as a model of higher human cognitive functions. Noradrenergic receptors play a modulatory role in many nerve functions, including vigilance, attention, reward, learning and memory. The present study aimed at studying the effects of separate or combined systemic administration of the alpha1-adrenergic antagonist prazosin (1 and 2 mg/kg) and beta-blocker propranolol (5 and 20 mg/kg) on the hippocampus-dependent learning in the active allothetic place avoidance (AAPA) task. Both centrally active drugs impaired spatial learning when administered together, exerting no effect in separate applications. Locomotion was impaired only in a combined application of higher doses of both drugs (2 mg/kg prazosin and 20 mg/kg propranolol). These results suggest an in vivo interaction between these two types of receptors in spatial navigation regulation.

• MeSH
• alfa blokátory aplikace a dávkování   farmakologie   MeSH
• analýza rozptylu MeSH
• beta blokátory aplikace a dávkování   farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• fixní kombinace léků MeSH
• krysa rodu Rattus MeSH
• pohybová aktivita účinky léků   MeSH
• poruchy učení chemicky indukované   MeSH
• potkani Long-Evans MeSH
• prazosin aplikace a dávkování   farmakologie   MeSH
• propranolol aplikace a dávkování   farmakologie   MeSH
• učení vyhýbat se účinky léků   MeSH
• vnímání prostoru účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa blokátory MeSH
• beta blokátory MeSH
• fixní kombinace léků MeSH
• prazosin MeSH
• propranolol 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.

• Klíčová slova
• Morris Water Maze (MWM), cognitive deficit, learning and memory, psychotic disorders, schizophrenia, spatial behavior, spatial navigation, virtual reality environment,
• Publikační typ
• časopisecké články MeSH

Nogo-A protein is an important inhibitor of axonal growth, which also regulates neuronal plasticity in the CNS. Mutations in the gene encoding Nogo-A or abnormalities in Nogo-A expression are linked to neuropsychiatric disorders such as schizophrenia. The present study assesses the impact of constitutively reduced expression of Nogo-A on place navigation in a novel transgenic rat model. Two spatial paradigms were used: (1) A battery of tests in the Carousel maze requiring continuous processing of spatial information with increasing demands for the segregation of reference frames and behavioral flexibility and (2) a delayed-matching-to-place version of the Morris water maze (MWM), which requires place navigation and is sensitive to deficits in one-trial-encoded place representation. The Carousel maze testing revealed a subtle but significant impairment in management of reference frames. Matching-to-place learning in the Morris water maze was unaffected, suggesting an intact representation of an unmarked goal. Our results show that Nogo-A deficiency leads to cognitive deficit in processing of the reference frames. Such a deficit may be the result of neuro-developmental alterations resulting from Nogo-A deficiency.

• Klíčová slova
• Cognitive coordination, Nogo-A, Spatial mazes, Spatial navigation, Transgenic rat model,
• MeSH
• bludiště - učení fyziologie   MeSH
• down regulace * MeSH
• genový knockdown MeSH
• krysa rodu Rattus MeSH
• myelinové proteiny genetika   metabolismus   MeSH
• Nogo proteiny MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• prostorové chování fyziologie   MeSH
• učení vyhýbat se fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• myelinové proteiny MeSH
• Nogo proteiny MeSH
• Rtn4 protein, rat MeSH Prohlížeč

Neurotransmitter substrate of spatial cognition belongs to current topics in behavioral neuroscience. The present study examined the effects of serotonin depletion with p-chlorophenylalanine on learning of rats in active place avoidance, a spatial task requiring allothetic mapping and cognitive coordination and highly dependent upon hippocampus. Serotonin depletion transiently increased locomotor activity in response to footshocks, but it did not change the avoidance efficiency measured by three spatial parameters. These results suggest that serotonin neurotransmission is not crucial for cognitive coordination and allothetic learning, i.e. the processes, which are crucial for active place avoidance performance.

• MeSH
• antagonisté serotoninu farmakologie   MeSH
• fenklonin farmakologie   MeSH
• kognice účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• pohybová aktivita účinky léků   fyziologie   MeSH
• potkani Long-Evans MeSH
• serotonin metabolismus   MeSH
• učení vyhýbat se 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
• Názvy látek
• antagonisté serotoninu MeSH
• fenklonin MeSH
• serotonin MeSH