Dopaminergic modulation of striatal neuropeptides: differential effects of D1 and D2 receptor stimulation on somatostatin, neuropeptide Y, neurotensin, dynorphin and enkephalin.
Dopaminergic modulation of neuropeptides in rat striatum was investigated by examining the effects of prolonged D1 or D2 receptor stimulation on levels of somatostatin, neuropeptide Y, neurotensin, dynorphin and enkephalin. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were treated for 7 days with either the D1 agonist SKF 38393 (12.5 mg/kg/day) or the D2 agonist quinpirole (1 mg/kg/day). Two regimens of agonist treatment were compared: continuous infusion via osmotic pump implanted i.p. and intermittent (once daily) i.p. injection. Rats were sacrificed 3 h after the last injection and peptide levels measured in the striatum bilaterally by radioimmunoassay; alterations in peptide content were observed primarily in the denervated striatum. In comparison to values from lesioned, vehicle-treated controls, intermittent administration of SKF 38393 reduced somatostatin and neuropeptide Y (down 61% and 57%, respectively), increased neurotensin (up 105%) and dynorphin (up 184%) and had no effect on enkephalin; continuous SKF 38393 decreased neuropeptide Y by 39% but did not alter levels of the other peptides. Continuous quinpirole elevated somatostatin and neuropeptide Y levels (up 43% and 33%, respectively), but reduced the lesion-induced increases in both neurotensin (down 51%) and enkephalin (down 24%) content. Conversely, intermittent quinpirole decreased somatostatin (down 35%) and neuropeptide Y (down 27%), increased neurotensin content by 79% and had no effect on enkephalin. Dynorphin levels were not altered by either continuous or intermittent quinpirole. These findings reveal the complexity of dopaminergic influences on striatal neuropeptides.(ABSTRACT TRUNCATED AT 250 WORDS)
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892.
T M
TM
Engber
R C
RC
Boldry
S
S
Kuo
T N
TN
Chase
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003714:Denervation; D015259:Dopamine Agents / Q000494:pharmacology*; D004399:Dynorphins / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013004:Somatostatin / Q000378:metabolism*
D015259:Dopamine Agents; D004873:Ergolines; D009478:Neuropeptide Y; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D009496:Neurotensin; D013004:Somatostatin; D004744:Enkephalin, Methionine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004399:Dynorphins; D016627:Oxidopamine