Previous studies suggest that enhanced noradrenergic neurotransmission promotes functional recovery following cerebral lesions. The present study investigated whether systemic administration of an alpha(2)-adrenergic antagonist,
atipamezole, facilitates recovery following transient focal
cerebral ischemia in rats. The effect of
atipamezole therapy on recovery from
ischemia was compared with the effect of enriched-environment housing in rats.
Ischemia was induced by occlusion of the right middle cerebral artery (MCA) for 120 min using the intraluminal filament model. Daily
atipamezole treatment (1 mg/kg, subcutaneously) was started on day 2 after
ischemia induction and
drug administration stopped after 10 days. Another group of rats was housed in an enriched environment from day 2 following
ischemia induction until the end of the experiment. Several different behavioral tests were used to measure functional recovery during the 26 days following the induction of focal
cerebral ischemia. There was improved performance in the limb-placing test from the beginning of
atipamezole treatment to day 8, and in wheel-running in the foot-slip test on days 2 and 4. Enriched-environment housing facilitated recovery in the foot-slip test in a later phase of the test period (days 8 to 10). Discovery of a hidden platform in a water-maze task was also facilitated in rats housed in the enriched environment, but this was probably due to the increased swimming speed of these rats. The present data suggest that the alpha(2)-adrenergic antagonist,
atipamezole, facilitates sensorimotor recovery after focal
ischemia, but has no effect on subsequent water-maze tests assessing spatial learning and memory, when assessed 11 days after the cessation of
drug administration.