The effect of antagonism of adrenergic receptors on spatial learning in laboratory rats.

Spatial navigation is an important aspect of animal behavior, and is often regarded as a model of higher cognitive functions, e.g. declarative memory. It can be easily assessed by various behavioral tasks ("mazes"), and compared even across different species. Therefore, spatial tasks are especially suitable for evaluating potential psychoactive drugs in an animal model. This work deals mainly with noradrenergic neurotransmitter system and its influence on learning, memory and spatial behavior. The experimental part focuses on effects of subtype-specific noradrenergic antagonists prazosin, idazoxan and propranolol, and also a D2 dopaminergic antagonist, sulpiride, in Active Allothetic Place Avoidance (AAPA) task, a novel spatial task, well suited for measuring both cognitive and motor impairments. Rats with high doses of noradrenergic antagonists show combined impairment in both cognitive and motor aspect of the task. β-adrenergic antagonist propranolol also causes specific cognitive impairment in a lower dose of 25 mg/kg, but it fails to induce long-term memory impairment when given after experimental session. Co-application of alpha-1 adrenergic and D2 dopaminergic antagonists, prazosin and sulpiride, causes a severe motor and cognitive impairment, even at doses that do not influence animal behavior when..

Learning and memory in Nogo-A knockdown rats

The Nogo-A protein belongs among the most important regulatory molecules in the brain, regulating development of neuronal and glial cells, axon guidance and adult synaptic plasticity. Although it has been studied mainly as an obstacle to axon regeneration after CNS injury, it plays a role in many pathological conditions, including neurodegenerative and neuropsychiatric diseases. This work offers a literature review of the current knowledge about functions of Nogo-A and related proteins, and then recapitulates the results of experiments focused on the impact on decreased expression of Nogo-A on behavior in a transgenic rat model. The most important finding is that the Carousel Maze performance, tapping higher cognitive functions such as cognitive coordination and cognitive flexibility, is remarkably impaired in this model, while other cognitive functions, such as spatial navigation and both spatial and non-spatial memory are spared in the Nogo-A deficient rats. The results are discussed in the context of a hypothesis linking Nogo-A mutations or abnormal expression to human schizophrenia. We conclude that the Nogo-A deficient rats constitute a very promising animal model of schizophrenia and deserve further attention

Learning and memory in Nogo-A knockdown rats

The Nogo-A protein belongs among the most important regulatory molecules in the brain, regulating development of neuronal and glial cells, axon guidance and adult synaptic plasticity. Although it has been studied mainly as an obstacle to axon regeneration after CNS injury, it plays a role in many pathological conditions, including neurodegenerative and neuropsychiatric diseases. This work offers a literature review of the current knowledge about functions of Nogo-A and related proteins, and then recapitulates the results of experiments focused on the impact on decreased expression of Nogo-A on behavior in a transgenic rat model. The most important finding is that the Carousel Maze performance, tapping higher cognitive functions such as cognitive coordination and cognitive flexibility, is remarkably impaired in this model, while other cognitive functions, such as spatial navigation and both spatial and non-spatial memory are spared in the Nogo-A deficient rats. The results are discussed in the context of a hypothesis linking Nogo-A mutations or abnormal expression to human schizophrenia. We conclude that the Nogo-A deficient rats constitute a very promising animal model of schizophrenia and deserve further attention. Powered by TCPDF (www.tcpdf.org

N-Methyl-d-Aspartate Receptor – Nitric Oxide Synthase Pathway in the Cortex of Nogo-A-Deficient Rats in Relation to Brain Laterality and Schizophrenia

It has been suggested that Nogo-A, a myelin-associated protein, could play a role in the pathogenesis of schizophrenia and that Nogo-A-deficient rodents could serve as an animal model for schizophrenic symptoms. Since changes in brain laterality are typical of schizophrenia, we investigated whether Nogo-A-deficient rats showed any signs of disturbed asymmetry in cortical N-methyl-D-aspartate (NMDA) receptor–nitric oxide synthase (NOS) pathway, which is reported as dysfunctional in schizophrenia. In particular, we measured separately in the right and left hemisphere of young and old Nogo-A-deficient male rats the expression of NMDA receptor subunits (NR1, NR2A and NR2B in the frontal cortex) and activities of NOS isoforms (neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) in the parietal cortex). In young controls, we observed right/left asymmetry of iNOS activity and three positive correlations (between NR1 in the left and NR2B laterality, between NR2B in the right and left sides, and between NR1 in the right side and nNOS laterality). In old controls, we found bilateral decreases in NR1, an increase in NR2B in the right side and two changes in correlations in the NR1–nNOS pathway. In young Nogo-A-deficient rats, we observed an increase in iNOS activity in the left hemisphere and two changes in correlations in NR1–nNOS and NR2A–eNOS, compared to young controls. Finally, we revealed in old Nogo-A-deficient animals, bilateral decreases in NR1 and one change in correlation between eNOS–iNOS, compared to old controls. Although some findings from schizophrenic brains did not manifest in Nogo-A-deficient rats (e.g., no alterations in NR2B), others did (e.g., alterations demonstrating accelerated ageing in young but not old animals, those occurring exclusively in the right hemisphere in young and old animals and those suggesting abnormal frontoparietal cortical interactions in young animals)