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Substance P Modulates Cocaine‐Evoked Dopamine Overflow in the Striatum of the Rat Brain
Author(s) -
KRAFT MADELYNE,
NOAILLES PIERRE,
ANGULO JESUS A.
Publication year - 2001
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2001.tb03561.x
Subject(s) - dopamine , striatum , neuroscience , chemistry , pharmacology , psychology , medicine
A bstract : To study the role of the neuropeptide substance P in modulating some of the effects of cocaine in the striatum, we administered cocaine to rats and measured preprotachykinin‐A (PPT‐A) messenger RNA and substance P peptide in the nigrostriatal pathway. We also measured the effect of a neurokinin‐1 (NK‐1) receptor antagonist on striatal cocaine‐evoked dopamine overflow by in vivo microdialysis in freely moving animals. Acute administration of cocaine to naive rats (15 mg/kg of body weight) increased preprotachykinin‐A mRNA levels in the dorsal and ventral aspects of the caudate putamen 4 hours after the intraperitoneal injection of cocaine. Concomitantly, in a separate group of animals, substance P peptide levels were decreased in the ventral caudate putamen and substantia nigra (38% below controls). In a separate experiment, infusion through the microdialysis probe of the neurokinin‐1 receptor antagonist L‐733,060 significantly decreased cocaine‐evoked striatal dopamine overflow (approximately 50% inhibition at 30 minutes after cocaine administration). Taken together, these results suggest a direct role for substance P in the modulation of some of the actions of cocaine in the striatum of the rat brain.