Differential effects of aprepitant, a clinically used neurokinin-1 receptor antagonist on the expression of conditioned psychostimulant versus opioid reward
Autor: | Padmanabhan Mannangatti, Lankupalle D. Jayanthi, Santhanalakshmi Sundaramurthy, Sammanda Ramamoorthy |
---|---|
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Morpholines Pharmacology Motor Activity Article 03 medical and health sciences Mice 0302 clinical medicine Cocaine Neurokinin-1 Receptor Antagonists Reward Dopamine Tachykinin receptor 1 Conditioning Psychological Medicine Animals Amphetamine Aprepitant Morphine business.industry musculoskeletal neural and ocular physiology Antagonist Association Learning Conditioned place preference Analgesics Opioid Mice Inbred C57BL 030104 developmental biology Monoamine neurotransmitter Opioid Central Nervous System Stimulants business 030217 neurology & neurosurgery Locomotion medicine.drug |
Zdroj: | Psychopharmacology. 234(4) |
ISSN: | 1432-2072 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |