Activation of central neurokinin-1 receptors induces reinstatement of cocaine-seeking behavior.
A number of neurochemical systems have been implicated in mediating relapse to drug-seeking behavior. Substance P (SP) is a neuropeptide that interacts with some of these systems, suggesting a possible role for SP and its preferred receptor, the neurokinin-1 (NK-1) receptor, in the mediation of relapse. In this study, we examined whether selective activation of NK-1 receptors induces reinstatement of cocaine-seeking behavior, and whether endogenous activity at these receptors is involved in mediating cocaine-induced reinstatement. For each experiment, rats were trained to self-administer cocaine for 8--10 days, and following a period of extinction, tests for reinstatement were given. To examine the effects of NK-1 receptor activation on reinstatement of cocaine-seeking behavior, animals received an intracerebroventricular (ICV) infusion of the selective NK-1 receptor agonist, [Sar(9)Met(O(2))(11)]-SP (0, 1, 3 microg), immediately prior to the test session. To examine the role of endogenous NK-1 receptor activity on cocaine-induced reinstatement, rats were pretreated with ICV infusions of the selective NK-1 receptor antagonists, RP 67580 (0, 0.1, 0.5, 2.5 nmol) or GR 82334 (0, 2, 10, 50 pmol), prior to systemic priming injections of cocaine (10mg/kg or 20mg/kg; i.p.). The results showed that [Sar(9)Met(O(2))(11)]-SP induced reinstatement of cocaine-seeking behavior, but that RP 67580 and GR 82334 had no effect on cocaine-induced reinstatement. These findings suggest that while activation of NK-1 receptors is capable of inducing reinstatement of cocaine-seeking behavior, endogenous activity at these receptors is not involved in mediating the priming effects of cocaine on reinstatement of drug-seeking behavior.
Placenza
Franca M
FM
Department of Psychology, University of Toronto, Toronto, Ont., Canada M5S 3G3.
Vaccarino
Franco J
FJ
Fletcher
Paul J
PJ
Erb
Suzanne
S
D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D054833:Isoindoles; D008297:Male; D010803:Physalaemin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism*; D012008:Recurrence; D012646:Self Administration
D007211:Indoles; D054833:Isoindoles; D018040:Receptors, Neurokinin-1; C079014:GR 82334; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D010803:Physalaemin; D003042:Cocaine