Topographical organization of opioid peptide precursor gene expression following repeated apomorphine treatment in the 6-hydroxydopamine-lesioned rat.
Many studies have previously described changes in preproenkephalin-A (PPE-A) and preproenkephalin-B (PPE-B) gene expression in the striatum of the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (both with or without dopamine replacement treatment). To date, these studies have either taken the striatum as a whole or have focused on a single subregion of the striatum. However, the striatum is organized into anatomically discrete parallel circuits serving different functions (motor, associative, and limbic). We have therefore employed in situ hybridization to examine the detailed topography of changes in opioid precursor expression following dopamine depletion and subsequent treatment with apomorphine (5 mg/kg twice daily for 10 days). In the untreated 6-OHDA-lesioned striatum PPE-A expression was elevated only in the dorsal (sensorimotor) caudate-putamen. Following apomorphine treatment PPE-A mRNA levels were further raised in the sensorimotor striatum (</=77%) and approximately doubled and tripled in the ventral caudate-putamen (associative) and nucleus accumbens (limbic), respectively. These subsequent elevations were mostly restricted to rostral portions of the striatum. Although unchanged following vehicle treatment, PPE-B gene expression in the lesioned caudate-putamen (sensorimotor and associative) was elevated some 30-fold by apomorphine treatment. A smaller rise (fivefold) was seen in rostral regions of the lesioned nucleus accumbens. Thus, differential regulation of opioid peptide transmission exists in motor, limbic, and associative regions of the striatum and may contribute to the generation of motor and cognitive disturbances following long-term treatment of the dopamine-depleted striatum.
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Division of Neuroscience, 1.124 Stopford Building, School of Biological Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, United Kingdom.
Henry
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Crossman
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Brotchie
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D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004745:Enkephalins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011498:Protein Precursors / Q000096:biosynthesis*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
D004745:Enkephalins; D011498:Protein Precursors; D016627:Oxidopamine; C033660:preproenkephalin; D001058:Apomorphine