Effects of anti-Parkinsonian drugs on neurobehavioural changes induced by bilateral 6-hydroxydopamine lesions in rats.
1. Effects of anti-Parkinsonian drugs on neurobehavioural changes induced by bilateral lesions of dopaminergic neurons were investigated in rats. 2. Dopaminergic neurons in rats were lesioned bilaterally by injection of 6-hydroxydopamine (6-OHDA; 8 micrograms) into the medial forebrain bundle at the level of the posterolateral hypothalamus. As a result, a decrease in locomotor activity and marked catalepsy and prolongation of grasping time were observed. 3. Levodopa, talipexole, bromocriptine and theophylline dose-dependently antagonized the decrease in locomotor activity induced by bilateral 6-OHDA lesions. These drugs also showed antagonistic effects on the appearance of catalepsy and prolongation of grasping time induced by bilateral 6-OHDA lesions. In contrast, trihexyphenidyl showed no antagonizing effect on the neurobehavioural changes induced by 6-OHDA lesions at any concentration tested. 4. Combined treatment with levodopa and talipexole antagonized the neurobehavioural changes induced by bilateral 6-OHDA lesions, whereas no marked changes were observed when either drug was administered separately. The same findings were noted with the simultaneous use of either levodopa (2 mg/kg) and theophylline (2 mg/kg) or talipexole (0.005 mg/kg) and theophylline (2 mg/kg). 5. These results indicate that this model may be useful for estimating the effects of drugs in the treatment of Parkinson's disease.
Hayakawa
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Sugimoto
Y
Y
Chen
Z
Z
Fujii
Y
Y
Kamei
C
C
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001381:Azepines / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007150:Immunohistochemistry; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000503:physiopathology; D011596:Psychomotor Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000627:therapeutic use; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D000978:Antiparkinson Agents; D001381:Azepines; D007980:Levodopa; C024763:talipexole; D016627:Oxidopamine; D013806:Theophylline; D014446:Tyrosine 3-Monooxygenase