Neurokinin receptors modulate the neurochemical actions of cocaine.
The psychostimulant cocaine is an indirect agonist that increases synaptic dopamine (DA) by binding with high affinity to the DA transporter (DAT) and blocking the active transport of synaptic DA back into the terminal. The resulting increase in extracellular DA alters postsynaptic activity in the circuitry of the basal ganglia. This study examines the role of neurokinin receptors on cocaine-evoked DA overflow in the striatum. Male Sprague-Dawley rats (n = 8) were treated with cocaine (10 mg/kg body weight i.p.) acutely or chronically. The pattern of DA release was assessed using in vivo microdialysis. In separate experiments two different neurokinin-1 (NK-1) receptor antagonists (D-Arg(1), D-Pro(2), D-Trp(7,9), Leu(11), or L-733,060) were perfused via the microdialysis probe for one hour in awake and freely moving animals that were subsequently injected i.p. with cocaine. Throughout the procedure, DA release was monitored at 1/2-hour intervals at a flow rate of 1 microl/min. In the groups of rats preperfused with NK-1 antagonists into the striatum, the cocaine-evoked release of DA was significantly reduced. This result suggests a significant role for the NK-1 receptor in the striatal response to acute and chronic cocaine administration.
Noailles
P-A H
PA
Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10021, USA.
Angulo
J A
JA
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology*
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D003042:Cocaine; D004298:Dopamine