Chronic sensitization to serotonin 1A and 7 receptors agonist 8-OH-DPAT induces compulsive checking and perseverative behavior. As such, it has been used to model obsessive-compulsive disorder (OCD)-like behavior in mice and rats. In this study, we tested spatial learning in the 8-OH-DPAT model of OCD and the effect of co-administration of memantine and riluzole-glutamate-modulating agents that have been shown to be effective in several clinical trials. Rats were tested in the active place avoidance task in the Carousel maze, where they learned to avoid the visually imperceptible shock sector. All rats were subcutaneously injected with 8-OH-DPAT (0.25 mg/kg) or saline (control group) during habituation. During acquisition, they were pretreated with riluzole (1 mg/kg), memantine (1 mg/kg), or saline solution 30 min before each session and injected with 8-OH-DPAT ("OH" groups) or saline ("saline" groups) right before the experiment. We found that repeated application of 8-OH-DPAT during both habituation and acquisition significantly increased locomotion, but it impaired the ability to avoid the shock sector. However, the application of 8-OH-DPAT in habituation had no impact on the learning process if discontinued in acquisition. Similarly, memantine and riluzole did not affect the measured parameters in the "saline" groups, but in the "OH" groups, they significantly increased locomotion. In addition, riluzole increased the number of entrances and decreased the maximum time avoided of the shock sector. We conclude that monotherapy with glutamate-modulating agents does not reduce but exacerbates cognitive symptoms in the animal model of OCD.

• Klíčová slova
• 8-OH-DPAT, memantine, memory, obsessive-compulsive disorder, riluzole, spatial learning,
• MeSH
• 8-hydroxy-2-(di-N-propylamino)tetralin škodlivé účinky   farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• krysa rodu Rattus MeSH
• memantin farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• obsedantně kompulzivní porucha * chemicky indukované   farmakoterapie   patofyziologie   MeSH
• paměť účinky léků   MeSH
• potkani Long-Evans MeSH
• prostorové učení účinky léků   MeSH
• riluzol farmakologie   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
• 8-hydroxy-2-(di-N-propylamino)tetralin MeSH
• memantin MeSH
• riluzol MeSH

The evolution of the vertebrate eye remains so far unresolved. Amphioxus frontal eye pigment cells and photoreceptors were proposed to be homologous to vertebrate photoreceptors and retinal pigmented epithelium, based on ultrastructural morphology and gene expression analysis in B. floridae. Here, we present comparative molecular data using two additional amphioxus species, a closely related B. lanceolatum, and the most divergent A. lucayanum. Taking advantage of a unique set of specific antibodies we characterized photoreceptors and putative interneurons of the frontal eye and investigated its neuronal circuitry. Our results corroborate generally conserved molecular fingerprint among cephalochordate species. Furthermore, we performed pharmacological perturbations and found that the Notch signaling pathway, a key regulator of retina development in vertebrates, is required for correct ratios among frontal eye cell types. In summary, our study provides a valuable insight into cell-type relationships in chordate visual organs and strengthens the previously proposed homology between amphioxus frontal eye and vertebrate eyes.

• Klíčová slova
• Notch signaling, chordates, eye evolution, gene expression, interneurons, light detection, photoreceptors, vision,
• Publikační typ
• časopisecké články MeSH