Modulation of quinpirole-induced compulsive-like behavior in rats by environmental changes: implications for OCD...

Rats treated chronically with the D2-3 dopamine agonist quinpirole were previously proposed as an animal model of obsessive-compulsive disorder (OCD) since their behavior is based on repeated, compulsive-like persistent traveling between a few places in the open field. The aim of the present study was to determine properties of the physical environment that shape such behavior. For this, quinpirole-treated rats were first exposed to an arena with an array of objects (landmarks) and after the development of compulsive-like behavior, the arena was manipulated by multiplying the number of objects, changing their spacing, relocating object array, or removing the objects.

When the number of objects was retained but they were spaced further apart, rat routes converged at 1-2 of the objects and at the corner at which the rats had been introduced into the arena (start corner). When object spacing was retained but their number was increased, the rats traveled between the objects with the routes converging only at the start corner. Finally, when object array was relocated to different places within the arena, the rats extended their routes from the start corner to the object array, regardless of array location.

Quinpirole-treated rats organized and updated their progression primarily according to the proximal layout of landmarks, but did so with excessive repetitions compared with saline-treated rats. The behavior of quinpirole-treated rats paralleled human OCD rituals that are linked to the immediate physical environment, featuring an excessive rate of performance. Finally, when only a few objects were present, they were perceived by the rats as positional cues (beacons) that routes converged at them. In contrast, in the presence of many objects, the routes passed between the objects as if using them as directional cues.