Effects of short- and long-acting dopamine agonists on sensitized dopaminergic neurotransmission in rats with unilateral 6-OHDA lesions.
The effects of short and long-acting dopamine agonists on sensitized dopaminergic transmission in an animal model of Parkinson's disease were investigated. Rats with 6-hydroxydopamine (6-OHDA) lesions of the left nigrostriatal dopaminergic pathway were pre-exposed i.p. to 50 mg/kg methyl levodopa for 10 days. After a 7-day withdrawal period, these animals were treated with saline i.p., 0.05 mg/kg apomorphine s.c., or 0.5 mg/kg cabergoline i.p., once daily for 7 days. On the 8th day, rats in each treatment group received a challenge dose of 0.05 mg/kg apomorphine or saline s.c. The temporal changes in the number of rotations away from the 6-OHDA lesion side were evaluated after the challenge. The apomorphine challenge increased the number of rotations more markedly in the apomorphine pretreated rats than in the other pretreatment groups. In cabergoline pretreated rats, the number of rotations was significantly lower than that of saline-pretreated animals. Pretreatment with saline did not alter the apomorphine sensitivity of rotational behavior. These findings suggest that the repeated administration of long-acting dopamine agonists may reduce sensitized dopaminergic transmission in dopamine-depleted rats, whereas short-acting ones may further enhance sensitization of the transmission process.
Kashihara
K
K
Department of Neurology, Okayama Kyokuto Hospital, Kurata, Japan. kkashi@kyokuto.or.jp
Manabe
Y
Y
Murakami
T
T
Abe
Koji
K
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D000077465:Cabergoline; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D004336:Drug Antagonism; D004873:Ergolines / Q000494:pharmacology*; D007980:Levodopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D004873:Ergolines; D007980:Levodopa; D016627:Oxidopamine; D000077465:Cabergoline; C035420:levodopa methyl ester; D001058:Apomorphine