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.
- 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
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.
- 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
RATIONALE: There is a persistent pressing need for valid animal models of cognitive and mnemonic disruptions (such as seen in Alzheimer's disease and other dementias) usable for preclinical research. OBJECTIVES: We have set out to test the validity of administration of biperiden, an M1-acetylcholine receptor antagonist with central selectivity, as a potential tool for generating a fast screening model of cognitive impairment, in outbred Wistar rats. METHODS: We used several variants of the Morris water maze task: (1) reversal learning, to assess cognitive flexibility, with probe trials testing memory retention; (2) delayed matching to position (DMP), to evaluate working memory; and (3) "counter-balanced acquisition," to test for possible anomalies in acquisition learning. We also included a visible platform paradigm to reveal possible sensorimotor and motivational deficits. RESULTS: A significant effect of biperiden on memory acquisition and retention was found in the counter-balanced acquisition and probe trials of the counter-balanced acquisition and reversal tasks. Strikingly, a less pronounced deficit was observed in the DMP. No effects were revealed in the reversal learning task. CONCLUSIONS: Based on our results, we do not recommend biperiden as a reliable tool for modeling cognitive impairment.
- MeSH
- Alzheimerova nemoc psychologie MeSH
- antagonisté muskarinových receptorů farmakologie MeSH
- biperiden farmakologie MeSH
- bludiště - učení účinky léků MeSH
- chování zvířat účinky léků MeSH
- kognitivní dysfunkce psychologie MeSH
- krátkodobá paměť účinky léků MeSH
- krysa rodu rattus * MeSH
- modely nemocí na zvířatech * MeSH
- poruchy paměti psychologie MeSH
- potkani Wistar MeSH
- reverzní učení 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
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.
- 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
- učení vyhýbat se účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Schizophrenia is a devastating disorder affecting 1 % of the world's population. An important role in the study of this disease is played by animal models. Since there is evidence that acute psychotic episodes can have consequences on later cognitive functioning, the present study has investigated the effects of a single systemic application of higher doses of (+)MK-801 (3 mg/kg and 5 mg/kg) to adult male Long-Evans rats from the Institute's breeding colony on delayed testing in the active place avoidance task with reversal on the Carousel (a rotating arena). Besides significant mortality due to the injections, a disruption of procedural functions in active place avoidance, after the dose 5 mg/kg was observed. It was concluded that Long-Evans rats from our breeding colony do not represent a suitable biomodel for studying the effects of single high-dose NMDA antagonists.
- MeSH
- antagonisté excitačních aminokyselin aplikace a dávkování toxicita MeSH
- dizocilpinmaleát aplikace a dávkování toxicita MeSH
- kognitivní poruchy chemicky indukované psychologie MeSH
- krysa rodu rattus MeSH
- potkani Long-Evans MeSH
- psychomotorický výkon účinky léků MeSH
- reverzní učení účinky léků MeSH
- toxické psychózy psychologie MeSH
- učení vyhýbat se účinky léků MeSH
- úniková reakce účinky 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
- práce podpořená grantem MeSH
