Postnatal administration of D1 dopamine agonist reverses neonatal dopaminergic lesion-induced changes in striatal enkephalin and substance P systems.
The present study examined the effects of postnatal dopamine (DA) receptor stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP) systems of basal ganglia of rats, lesioned as neonates with 6-hydroxydopamine (6-OHDA, intracisternally) on the third postnatal day. D1 agonist, SKF-38393 or D2 agonist, LY-171555 (also known as quinpirole) was administered s.c. twice daily for 14 days, beginning 24 h after 6-OHDA administration. The animals were sacrificed at 60 days of age, and the concentrations of striatal DA, SP, and ME were determined by HPLC or radioimmunoassay. As expected, 6-OHDA induced a severe loss of DA, an increase in ME, and a decrease in SP. SKF-38393, but not, quinpirole significantly reversed the lesion-induced changes in ME and SP levels. The results indicate an important role for D1 receptors in the postnatal development of ME and SP systems in the striatum. These studies are relevant to our further understanding of potential early interventions in the progression and expression of DA deficiency states such as Parkinsonism and Lesch-Nyhan disease.
Sivam
Subbiah P
SP
Department of Pharmacology and Toxicology, Indiana University School of Medicine-Northwest, 3400 Broadway, Gary, IN 46408, USA. ssivam@iun.edu
Cox
Jeffrey
J
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development / Q000293:injuries / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D004745:Enkephalins / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D011247:Pregnancy; D019257:Quinpirole / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013373:Substance P / Q000378:metabolism*
D018663:Adrenergic Agents; D004745:Enkephalins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D013373:Substance P; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D004298:Dopamine