Substance P modulates cocaine-evoked dopamine overflow in the striatum of the rat brain.
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.
Kraft
M
M
Department of Biological Sciences, Hunter College, City University of New York, 695 Park Avenue, New York, New York 10021, USA.
Noailles
P
P
Angulo
J A
JA
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D011498:Protein Precursors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D015320:Tachykinins / Q000494:pharmacology
D018765:Dopamine Uptake Inhibitors; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D003042:Cocaine; D004298:Dopamine