NDLI: Differential effects of aprepitant, a clinically used neurokinin-1 receptor antagonist on the expression of conditioned psychostimulant versus opioid reward

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Differential effects of aprepitant, a clinically used neurokinin-1 receptor antagonist on the expression of conditioned psychostimulant versus opioid reward

Content Provider	Springer Nature Link
Author	Mannangatti, Padmanabhan Sundaramurthy, Santhanalakshmi Ramamoorthy, Sammanda Jayanthi, Lankupalle D.
Copyright Year	2016
Abstract	Neurokinin-1 receptor (NK1R) signaling modulates behaviors associated with psychostimulants and opioids. Psychostimulants, such as amphetamine (AMPH) and cocaine, bind to monoamine transporters and alter their functions. Both dopamine and norepinephrine transporters are regulated by NK1R activation suggesting a role for NK1R mediated catecholamine transporter regulation in psychostimulant-mediated behaviors.The effect of in vivo administration of aprepitant (10 mg/kg) on the expression of AMPH (0.5 and 2 mg/kg) and cocaine (5 and 20 mg/kg)-induced conditioned place preference (CPP) as well as locomotor activation was examined in C57BL/6J mice. The effect of aprepitant on morphine (1 and 5 mg/kg)-induced CPP was also examined to identify the specific actions of aprepitant on psychostimulant versus opioid-induced behaviors.Aprepitant administration significantly attenuated the CPP expression and locomotor activation produced by AMPH and cocaine. In contrast, aprepitant significantly enhanced the expression of CPP produced by morphine while significantly suppressing the locomotor activity of the mice conditioned with morphine. Aprepitant by itself did not induce significant CPP or conditioned place aversion or locomotor activation or suppression.Attenuation of AMPH or cocaine-induced CPP and locomotor activation by aprepitant suggests a role for NK1R signaling in psychostimulant-mediated behaviors. Stimulation of morphine-induced CPP expression and suppression of locomotor activity of morphine-conditioned mice suggest differential effects of NK1R antagonism on conditioned psychostimulant versus opioid reward. Collectively, these findings indicate that clinically used NK1R antagonist, aprepitant may serve as a potential therapeutic agent in the treatment of psychostimulant abuse.
Starting Page	695
Ending Page	705
Page Count	11
File Format	PDF
ISSN	00333158
Journal	Psychopharmacology
Volume Number	234
Issue Number	4
e-ISSN	14322072
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-12-24
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Neurokinin-1 receptor Antagonist Aprepitant Amphetamine Cocaine Morphine Conditioned place preference Psychostimulants Opioids Drug abuse Neurosciences Pharmacology/Toxicology Psychiatry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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