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Interaction of serotonin-1A receptors with N-methyl-D-aspartate receptor: Implication to treatment and pathophysiology of schizophrenia
Puskarčíková, Jana ; Valešová, Věra (advisor) ; Stuchlík, Aleš (referee)
Schizophrenia is a serious mental disorder affecting about 1% of the world's population. Serotonin-1A (5-HT1A) receptors are found on dendrites, which are concentrated in and N-methyl-D-aspartate (NMDA) receptors. Current therapy has many side effects. Based hypoglutamaterg hypothesis of schizophrenia is the current strategy in the search for new drugs indirect activation of NMDA receptors. Direct activation of NMDA receptors leads to neuronal damage. The aim of the thesis was to determine whether NMDA receptors interact with 5-HT1A receptors as the molecular and the behavioral level. At the molecular level, we found that administration of 5-HT1A agonist receptors (8-OH-DPAT, tandospirone) leads to an increase/decrease the expression of subunits (GluN1, 2B), the NMDA receptor in the frontal cortex and hippocampus. At the behavioral level, we test for sensorimotor gating (Prepulz inhibition of startle response, PPI) we found that the administration of 8-OH-DPAT worse information processing. Tandospirone had no effect on PPI. Test anxiety measurement (ultrasonic vocalizations) showed that 8-OH-DPAT and tandospirone at high doses improves anxiety. The test for recognition memory (novel object recognition test, NORT) that tandospiron, at a lower dose improves recognition memory. 8-OH-DPAT had no effect level of...
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