Dopaminergic agonists and muscarinic antagonists improve lateralization in hemiparkinsonian rats in a novel exploratory Y-maze.
Parkinson's disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. Its primary clinical symptoms are akinesia, tremor, and rigidity, which usually start from one side, resembling the lateralization in hemiparkinsonian rats having 6-hydroxydopamine-induced unilateral lesion of the medial forebrain bundle. A novel exploratory Y-maze was designed to detect the lateralization of hemiparkinsonian rats in terms of biased turns in the maze. Dopamine agonists levodopa (L-3,4-dihydroxyphenylalanine, 10-30 mg/kg) and apomorphine (0.1-0.3 mg/kg), but not methamphetamine (0.5-2 mg/kg), improved the lateralization in the rat model. However, high doses of the dopamine agonists, 30 and 0.3 mg/kg, respectively, caused small movements in the arms that seemed to parallel the increase in counts per turn in the Y-maze. Interestingly, the muscarinic antagonists trihexyphenidyl and scopolamine improved lateralization moderately, while increasing total turns, an index of locomotive activity. (-)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) (0.3 mg/kg), an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, increased total counts, but did not alleviate the lateralization. The alpha2-adrenoceptor antagonist idazoxan (1 and 10 mg/kg) and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (1 and 3 mg/kg), a non-NMDA glutamate receptor antagonist, did not affect any of the indices. These findings suggest that the clinical action of drugs on unbalanced movement in PD could be predicted by measuring their effects on lateralization of the 6-hydroxydopamine-lesioned rat model in this exploratory Y-maze.
Nakagawa
Makoto
M
Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba-shi, Ibaraki 300-2635, Japan. m-nakagawa@hhc.eisai.co.jp
Ohgoh
Makoto
M
Nishizawa
Yukio
Y
Ogura
Hiroo
H
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use*; D007839:Functional Laterality / Q000187:drug effects; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000978:Antiparkinson Agents; D018680:Cholinergic Antagonists; D018491:Dopamine Agonists; D018727:Muscarinic Antagonists; D007980:Levodopa; D016291:Dizocilpine Maleate; D016627:Oxidopamine