AbstractBackground and Purpose: Abnormalities in visual perception are associated with a number of neurological diseases, particularly schizophrenia, and may represent a novel avenue of treatment for such disorders. However, translatability of pre-clinical models of psychosis to patient populations is lacking, particular with regards to the study of perception in these models. The purpose of the present study was to investigate the effect of pro-psychotic and schizophrenia-associated compounds on the ability of rats to perform a task of visual integration by proximity.
Experimental Approach: Rats were trained in a touchscreen operant environment to perform a visual discrimination between stimuli that were composed of rows of dots differing only in their relative horizontal and vertical proximity, a process thought to measure visual integration. Animals were then tested under the influence of glutamatergic (memantine, NVP-AAM077, CP-101,606), serotonergic (psilocybin, ketanserin) and dopaminergic (D-amphetamine, methylphenidate, haloperidol) compounds while performing the visual discrimination task with a range of altered stimuli.
Key Results: The GluN2B-selective NMDA antagonist CP-101,606 impaired perceptual grouping on the task in a dose-dependent manner, while a GluN2A-selective antagonist showed increased ability on the task through a mechanism independent of grouping. Paradoxical results were encountered in agonist/antagonist drug pairings; the dopamine-releasing agent D-amphetamine and the antipsychotic haloperidol both impaired perceptual grouping, whereas both agonist and antagonist at 5HT-2A, psilocybin and ketanserin, respectively increased accuracy, in a non-stimulus-specific manner, suggesting an underlying mechanism potentially distinct from perceptual grouping enhancement.
Conclusions and Implications: My findings add to the evidence that NMDA antagonists are strongly associated with alterations in visual cognition. They indicate GluN2B antagonism results in an impairment of visual grouping by proximity, whereas GluN2A antagonism increases task accuracy though in a non stimulus-specific manner. The findings also indicate potentially paradoxical interactions of monoaminergic pharmacology on visual perception, which will require investigation to understand further.
|Date of Award||24 Jun 2016|
|Supervisor||Eamonn P Kelly (Supervisor) & Pim Drinkenburg (Supervisor)|