Neural circuits underlying ketamine induced oculomotor behavior in the rat: 2-deoxyglucose studies

Time-related changes in oculomotor function and of metabolic activity patterns in selected brain networks, as assessed by the quantitative 2-deoxyglucose technique, were investigated in Long-Evans rats following intraperitoneal administration of a ketamine anesthetic dose. During ketamine-induced anesthesia a nystagmic-like behavior was present, characterized by unidirectional slow ocular drifts with superimposed paroxystic bursts of quick (saccadic-like) eye movements; all quick movements were executed in the horizontal direction, were strictly confined to an ocular hemifield of vision, and were followed by a backward (centripetal) drift. A metabolic hyperactivity was found in the dorsomedial shoulder region of the frontal cortex, corresponding to the rat saccadic cortical generator area, whereas functional activity levels were decreased in cerebellum and in several brainstem regions, including portions of the reticular formation and medial vestibular nuclei, putatively indicated as the locus of the oculomotor neural integrator. Starting 2 h after drug injection, a gradual recovery of oculomotor function occurred, with the disappearance of slow ocular drifts. However, an almost uninterrupted sequence of individual saccades was still present. Significant metabolic increases were found at this time in the cingulate and frontal cortex, basal ganglia, superior colliculus, paramedian reticular formation and oculomotor nuclei, the cerebellar vermis and paraflocculus. In medial vestibular nuclei, metabolic levels were undistinguishable from controls. These results suggest different concentration-dependent actions of ketamine on cortical and subcortical circuits involved in saccade generation and gaze holding. These effects are likely to be related at least in part to antagonism of N-methyl-D-aspartate receptor-mediated functions.