Effects of the neuropeptide S receptor antagonist RTI-118 on abuse-related facilitation of intracranial self-stimulation produced by cocaine and methylenedioxypyrovalerone (MDPV) in rats

被引：16

作者：

Bonano, Julie S. ^{[1
]}

Runyon, Scott P. ^{[2
]}

Hassler, Carla ^{[2
]}

Glennon, Richard A. ^{[3
]}

Negus, S. Stevens ^{[1
]}

机构：

[1] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA

[2] Res Triangle Inst, Organ & Med Chem, Res Triangle Pk, NC 27709 USA

[3] Virginia Commonwealth Univ, Dept Med Chem, Richmond, VA 23298 USA

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2014年 / 743卷

关键词：

Neuropeptide S; RTI-118; Cocaine; Methylenedioxypyrovalerone; Intracranial self-stimulation; KAPPA-OPIOID AGONISTS; SEEKING BEHAVIOR; RHESUS-MONKEYS; BATH SALTS; PAIN; NEUROBIOLOGY; PHARMACOLOGY; CATHINONES; SYSTEM; BRAIN;

D O I：

10.1016/j.ejphar.2014.09.006

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Neuropeptide S (NPS) is a neurotransmitter that activates the NPS receptor to modulate biological functions including anxiety-like behaviors, feeding, and drug reinforcement. RTI-118 is a novel NPS receptor antagonist that decreased cocaine self-administration in rats at doses that had little or no effect on food-maintained responding. To build on these previous findings, this study examined effects of RTI-118 on cocaine-induced facilitation of intracranial self-stimulation (ICSS) in rats. To provide a context for data interpretation, effects of RTI-118 were compared to effects of the kappa opioid receptor agonist U69,593, because the kappa opioid receptor is another peptide neurotransmitter receptor reported to modulate abuse-related cocaine effects. RTI-118 effects were also examined on ICSS facilitation produced by methyleneclioxypyrovalerone (MDPV), a novel designer drug of abuse with some cocaine-like effects. Male Sprague-Dawley rats (n=12) with electrodes targeting the medial forebrain bundle responded under a fixed-ratio 1 schedule for range of brain stimulation frequencies. Under control conditions, brain stimulation maintained a frequency-dependent increase in ICSS rates. Cocaine (1.0-10 mg/kg) and MDPV (3.2 mg/kg) facilitated ICSS. RTI-118 (3.2-32 mg/kg) alone produced little effect on ICSS but dose dependently blocked cocaine induced ICSS facilitation. U69,593 (0.25-0.5 mg/kg) also attenuated cocaine effects, but blockade of cocaine effects was incomplete even at a U69,593 dose that alone depressed ICSS. RTI-118 (32 mg/kg) failed to block MDPV-induced ICSS facilitation. These results support further consideration of NPS receptor antagonists as candidate treatments for cocaine abuse and provide evidence for differential effects of a candidate treatment on abuse related effects of cocaine and MDPV. (C) 2014 Elsevier B.V. All rights reserved,

引用

页码：98 / 105

页数：8

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