NMDA receptor antagonists distort visual grouping in rats performing a modified two-choice visual discrimination task.

Low doses of the NMDA receptor antagonists ketamine and phencyclidine impair visual grouping in rats, requiring higher signal quality to discriminate patterns, without affecting discrimination of undistorted images. Higher doses impair task performance even with clear images, linked to stereotypic behavior and impulsivity. A new rodent task using Glass patterns differentiates perceptual effects from motor or memory effects, enabling quantification of cognitive psychosis that translates to human psychometric functions.

Study at a glance

Abstract

Visual perception is impaired during pathological psychosis, which can be mimicked by NMDA receptor antagonists. However, the underlying mechanisms are poorly understood, partly due to limits of current rodent models for visual integration. The objectives of the study are (1) to develop a rodent task that can differentiate between effects on perception and nonspecific effects on task performance and (2) to test whether NMDA receptor antagonists affect visual perception in rats. We used an adaptation of Glass patterns to assess visual grouping in rats using a two-choice visual discrimination task in an infrared touch screen conditioning chamber. After rats learned to discriminate between a radial and a concentric bipole pattern, the ability to discriminate between these patterns was tested at various levels of distortion and a psychometric function was fit to obtain the maximum task performance and signal level needed for half-maximum performance. NMDA receptor antagonists ketamine and phencyclidine at low doses increased the signal quality needed to discriminate between the visual patterns, without affecting the ability to discriminate between undistorted images. At higher doses, the ability to perform the task even with undistorted images was impaired, which was associated with stereotypic behaviour and increased impulsivity. The Glass pattern-based visual grouping task is able to differentiate the effect of psychotomimetic NMDA receptor antagonists on visual perception from the effects on motor and memory functions. The half-maximum performance signal level allows quantification of cognitive psychosis in rodents, which can be translated to human psychometric functions and can be used in the development of more effective treatments.