Enhancement of the behavioral response to apomorphine administration following repeated treatment in the 6-hydroxydopamine-lesioned rat is temporally correlated with a rise in striatal preproenkephalin-B, but not preproenkephalin-A, gene expression.
Repeated dopamine receptor stimulation in the 6-hydroxydopamine (6-OHDA)-lesioned rat produces a marked enhancement in the behavioral response to a given dose of dopamine agonist. Such treatment also increases the synthesis of preproenkephalin-B (PPE-B) throughout the striatum and preproenkephalin-A (PPE-A) rostrally. To examine the relationship between these changes, 6-OHDA-lesioned rats were treated with apomorphine (5 mg/kg) twice-daily. Between 0.5 and 7 days treatment, behavior was monitored and the levels of PPE-A and PPE-B mRNA were determined by in situ hybridization. A single injection of apomorphine induced a well-known rotational response contraversive to the lesion (314 +/- 22 rotations h-1). However, with repeated injection, the response to apomorphine was markedly enhanced, being significantly higher on Days 3 (704 +/- 60 rotations h-1), 5 (1354 +/- 104 rotations h-1), and 7 (1680 +/- 117 rotations h-1). In the lesioned caudate-putamen, but not in the nucleus accumbens, PPE-B expression rose in a manner that was temporally correlated with the enhanced locomotor response to apomorphine. PPE-A expression in the lesioned striatum, significantly increased only after 7 days treatment, did not correlate with the behavioral response. In conclusion, PPE-B may contribute to the development of behavioral supersensitivity following repeated dopamine-replacement therapy in animal models of Parkinson's disease.
Duty
S
S
Neurodegenerative Diseases Research Centre, King's College London, United Kingdom.
Brotchie
J M
JM
D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006948:Hyperkinesis / Q000139:chemically induced* / Q000503:physiopathology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D011699:Putamen / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D012399:Rotation; D013997:Time Factors
D018663:Adrenergic Agents; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D016627:Oxidopamine; C033660:preproenkephalin; D001058:Apomorphine