Behavioral alterations after unilateral 6-hydroxydopamine lesions of the striatum. Effect of alpha-tocopherol.
6-Hydroxydopamine (6-OHDA) injected unilaterally into the striatum of rats induced contralateral circling, and increased the duration of stereotyped movements after subcutaneous (sc) injection of apomorphine both 3 and 13 weeks after surgery. Ten weeks after surgery, the spontaneous locomotor activity during 24 h of observation was decreased. Twelve weeks after 6-OHDA injection, the animals had difficulties in carrying out a spatial navigation task in the water maze when the submerged escape platform was moved to another position on each of four consecutive days. When learning to find a new platform position required switching behavior-strategies, latency and swim paths were increased because of significantly more perseverative crossings of the previous platform positions. Intraperitoneal (ip) injection of alpha-tocopherol for 8 days increased the ability of naive control animals to find the hidden platform positions in the water maze one week later. In intrastriatal sham-operated rats, 8 daily pre-injections of alpha-tocopherol significantly increased the duration and number of bursts of stereotyped movements during 30 min following a sc injection of apomorphine if measured 13 weeks after surgery. In 6-OHDA-lesioned rats, alpha-tocopherol prevented the increased response to apomorphine, reduced the apomorphine-induced circling at 3 and 13 weeks, and prevented the decrease in spontaneous locomotion at 10 weeks, as well as the perseverative platform crossings which are caused by an impairment in switching behavior-strategies in the navigation task 12 weeks after surgery. Alpha-Tocopherol has, however, no influence on 6-OHDA-induced changes in problem solving strategies. The used model reflects some of the pathological symptoms of Parkinson's disease, and it seems that alpha-tocopherol may be an effective drug in the early initial stages of the disease.
Heim
C
C
Department of Neuropharmacology and Physiology, Max-Planck-institute for Experimental Medicine, Göttingen, Germany.
Kolasiewicz
W
W
Kurz
T
T
Sontag
K H
KH
D018663:Adrenergic Agents / Q000633:toxicity*; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D007267:Injections; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects; D024502:alpha-Tocopherol / Q000494:pharmacology*
D018663:Adrenergic Agents; D018674:Adrenergic Antagonists; D000975:Antioxidants; D016627:Oxidopamine; D024502:alpha-Tocopherol; D001058:Apomorphine