D-Amphetamine reduces striatal substance P concentrations by presynaptic release of dopamine.
Single, but not repeated, doses of D-amphetamine sulfate cause dose-dependent reductions in substance P (SP) immunoreactive material within the rat striatum. A 10 mg/kg (i.p.) dose reduces SP levels from 1.37 to 0.97 pmol/10 mg tissue after 2 h. Similar reductions in striatal SP levels are observed after administration of methylphenidate (50 or 100 mg/kg). No changes in SP concentrations occur within the substantia nigra or hypothalamus after D-amphetamine. The amphetamine-induced decline in striatal SP is blocked by pretreating rats with alpha-methyl tyrosine methyl ester (225 mg/kg i.p.), or haloperidol (1, 3 or 10 mg/kg i.p.), or after the dopaminergic nigrostriatal tract has been lesioned using 6-hydroxydopamine. These data indicate that the mechanism by which D-amphetamine lowers striatal SP involves presynaptic release of dopamine from the terminals of nigrostriatal neurons.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009928:Organ Specificity; D051381:Rats; D013373:Substance P / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D008781:Methyltyrosines; D009419:Nerve Tissue Proteins; D013373:Substance P; D006220:Haloperidol; D003913:Dextroamphetamine; D004298:Dopamine