Selective activation of mesolimbic and mesocortical dopamine metabolism in rat brain by infusion of a stable substance P analogue into the ventral tegmental area.
Microinfusion of the metabolically stable substance P (SP) agonist, [pGlu5,MePhe8,Sar9]-SP5-11 (DiMe-C7), into the ventral tegmental area (VTA) of rat brain increased levels of the dopamine (DA) metabolite dihydroxyphenylacetic acid in the prefrontal cortex (+ 120%) and nucleus accumbens (+30%) but not in other regions of forebrain. In contrast, infusions of DiMe-C7 or SP into the lateral ventricles or microinfusions of SP into VTA failed to elicit increases in DOPAC levels in forebrain. DA levels were unaffected by SP or DiMe-C7 regardless of the route of administration. These data and previous studies suggest a role for endogenous SP in the modulation of mesocortical and mesolimbic DA neurones.
P J
PJ
Elliott
J E
JE
Alpert
M J
MJ
Bannon
S D
SD
Iversen
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D005625:Frontal Lobe / Q000187:drug effects*; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D010446:Peptide Fragments; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D010446:Peptide Fragments; D013373:Substance P; C032720:substance P (5-11), pGlu(5)-MePhe(8)-MeGly(9)-; D011761:Pyrrolidonecarboxylic Acid; D004298:Dopamine