Opposing effects of glutamatergic and GABAergic pharmacological manipulations on a visual perception task with relevance to schizophrenia

• Published in: Psychopharmacology Vol. 232; no. 21-22; pp. 3967 - 3976
• Main Authors: Talpos, John C., Riordan, John, Olley, Joseph, Waddell, Jason, Steckler, Thomas
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-11-2015; Springer; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Central nervous system agents; Conditioning, Operant - drug effects; Discrimination (Psychology) - drug effects; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists - pharmacology; GABA Modulators - pharmacology; Male; Neurobiology; Neurosciences; Original Investigation; Pharmacology/Toxicology; Photic Stimulation; Physiological aspects; Psychiatry; Psychomotor Performance - drug effects; Psychopharmacology; Rats; Receptors, GABA - drug effects; Receptors, Glutamate - drug effects; Receptors, N-Methyl-D-Aspartate - drug effects; Schizophrenia; Schizophrenic Psychology; Visual perception; Visual Perception - drug effects; Visual task performance; Touchscreen; Autism; Visual cortex; Rat; Schizophrenia; Visual integration; NMDA receptor
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-015-3964-4

Rationale
Numerous psychiatric disorders and neurodegenerative diseases have been associated with differences in visual perception, and it has been proposed that the treatment of these differences may represent a novel means to treat disorders like schizophrenia. Unfortunately, few methods exist to study visual perception in pre-clinical species.
Objective
The purpose of the present study was to adapt a task of visual integration by proximity with relevance to schizophrenia to a rodent touchscreen environment to determine the effects of glutamatergic and GABAergic compounds. In this way, we could evaluate the effects of common models of cognitive impairment, as well as the effects of net excitation versus inhibition, on a task of visual integration.
Method
Rats were trained to perform a visual discrimination where the stimuli were composed of rows of dots differing only in there horizontal and vertical proximity. Once stable performance had been achieved, animals were tested under the influence of glutamatergic or GABAergic drugs (ketamine, MK-801, PCP, memantine, chlordiazepoxide, or diazepam) while attempting to perform a visual discrimination with altered stimuli.
Results
Ketamine appeared to impair perceptual grouping in this paradigm, while the GABA agonist chlordiazepoxide enhanced grouping even in the presence of non-selective effects.
Conclusions
In general, these findings support the theory that NMDA antagonists may disrupt visual grouping by proximity and highlight a potential beneficial effect of enhanced GABA activity in perception. However, additional research will be required to confirm the stimulus selectivity of this effect, and the clinical significance of this approach.