Differential effect of the alpha2-adrenoceptor antagonist, atipamezole, in limb-placing task and skilled forepaw use following experimental stroke.
OBJECTIVE
Tbc present study compared tbc effect of chronic administration of the selective alpha2-adrenoceptor antagonist, atipamezole, on performance in behavioral tests that differ in motoric complexity in two experimental stroke models.


METHODS
Transient occlusion (120 min) of the middle cerebral artery (MCA) using the intraluminal method was used to produce corticostriatal infarcts and permanent occlusion of distal MCA by electrocoagulation was used to produce cortical infarcts. Chronic atipamezole treatment (1 mg/kg, s.c., once per day) was started 2 days after ischemia induction and continued until the end of the experiment, 35 days after ischemia induction. Behavioral performance of the operated rats was assessed 30 min after drug administration using the limb-placing test and Montoya's staircase test.


RESULTS
Atipamezole facilitated spontaneous recovery in the limb-placing task particularly in rats subjected to transient MCA occlusion. The analysis of retrieved pellets in Montoya's staircase test suggests that there is no recovery (Time effect, P > 0.05) in the use of the impaired forelimb (contralateral-to-lesion) following transient MCA occlusion, whereas there was some recovery following permanent MCA occlusion (Time effect, P < 0.001). The impairment was bilateral in rats subjected to transient MCA occlusion. Atipamezole treatment did not affect the use of the impaired forelimb to retrieve pellets following transient MCA occlusion, but there was a tendency to facilitate impaired forelimb use following permanent MCA occlusion (Time*Treatment interaction, P = 0.086).


CONCLUSIONS
Transient occlusion of the MCA produced a severe, long lasting, and bilateral deficit in skilled forelimb use. Permanent occlusion of the distal MCA was associated with less severe impairment, which was alleviated to some extent by administration of atipamezole. This is in contrast to spontaneous recovery and recovery-enhancing effects of atipamezole in the limb-placing test, particularly in the transient MCA occlusion model.
Butovas
S
S
Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland.
Lukkarinen
J
J
Virtanen
T
T
Jolkkonen
J
J
Sivenius
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005552:Forelimb; D007093:Imidazoles / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009043:Motor Activity; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole