Nitric oxide and substance dependence

Uzbay, I.T.; Oglesby, Michael

doi:10.1016/s0149-7634(00)00049-x

Cited by 109 publications

(19 citation statements)

References 106 publications

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“…Given this expression profile, the BV‐2 mouse microglial cell line was used to model the microglia, as these cells reproduce many of the responses of primary microglia, with high fidelity (Henn et al , ). TLR4 activation induces the downstream production of the inflammatory factor NO, which contributes to the development of neuropathic pain (Schmidtko et al , ) and drug addiction (Tayfun Uzbay and Oglesby, ; Toda et al , ).…”

Section: Resultsmentioning

confidence: 99%

Pharmacological characterization of the opioid inactive isomers (+)‐naltrexone and (+)‐naloxone as antagonists of toll‐like receptor 4

Wang

Zhang

Peng

et al. 2016

British J Pharmacology

139

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BACKGROUND AND PURPOSEThe toll-like receptor TLR4 is involved in neuropathic pain and in drug reward and reinforcement. The opioid inactive isomers (+)-naltrexone and (+)-naloxone act as TLR4 antagonists, reversing neuropathic pain and reducing opioid and cocaine reward and reinforcement. However, how these agents modulate TLR4 signalling is not clear. Here, we have elucidated the molecular mechanism of (+)-naltrexone and (+)-naloxone on TLR4 signalling. EXPERIMENTAL APPROACHBV-2 mouse microglial cell line, primary rat microglia and primary rat peritoneal macrophages were treated with LPS and TLR4 signalling inhibitors. Effects were measured using Western blotting, luciferase reporter assays, fluorescence microscopy and ELISA KEY RESULTS(+)-Naltrexone and (+)-naloxone were equi-potent inhibitors of the LPS-induced TLR4 downstream signalling and induction of the pro-inflammatory factors NO and TNF-α. Similarly, (+)-naltrexone or (+)-naloxone inhibited production of reactive oxygen species and increased microglial phagocytosis, induced by LPS. However, (+)-naltrexone and (+)-naloxone did not directly inhibit the increased production of IL-1β, induced by LPS. The drug interaction of (+)-naloxone and (+)-naltrexone was additive. (+)-Naltrexone or (+)-naloxone inhibited LPS-induced activation of IFN regulatory factor 3 and production of IFN-β. However, they did not inhibit TLR4 signalling via the activation of either NF-κB, p38 or JNK in these cellular models. CONCLUSIONS AND IMPLICATIONS(+)-Naltrexone and (+)-naloxone were TRIF-IFN regulatory factor 3 axis-biased TLR4 antagonists. They blocked TLR4 downstream signalling leading to NO, TNF-α and reactive oxygen species. This pattern may explain, at least in part, the in vivo therapeutic effects of (+)-naltrexone and (+)-naloxone. AbbreviationsAP-1, activator protein 1; IRF3, IFN regulatory factor 3; MD2, myeloid differentiation protein 2; MyD88, myeloid differentiation primary response 88; NBT, nitroblue tetrazolium; STAT, signal transducer and activator of transcription; TLR4, tolllike receptor 4; TRIF, TIR-domain-containing adapter-inducing IFN-β BJP British Journal of Pharmacology

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Section: Resultsmentioning

confidence: 99%

Pharmacological characterization of the opioid inactive isomers (+)‐naltrexone and (+)‐naloxone as antagonists of toll‐like receptor 4

Wang

Zhang

Peng

et al. 2016

British J Pharmacology

139

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“…It is suggested that chronic treatment with NOS inhibitors and FNZ would lead to prevention of GABA A receptor downregulation and/or glutamate receptor upregulation. There is evidence that NO is produced following activation of N -methyl- d -aspartate (NMDA) receptors (Garthwaite 2008; Uzbay and Oglesby 2001). Interestingly, many studies reveal the ability of NMDA receptor antagonists to attenuate tolerance to motor-impairing effects after long-term treatment with various drugs acting via the GABA A receptors.…”

Section: Discussionmentioning

confidence: 99%

The Importance of l-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice

et al. 2016

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The goal of the study was to investigate the effects of drugs modifying l-arginine:NO:cGMP pathway on the development of tolerance to flunitrazepam (FNZ)-induced motor impairment in mice. FNZ-induced motor incoordination was assessed on the 1st and 8th days of experiment, using the rotarod and chimney tests. It was found that (a) both a non-selective nitric oxide synthase (NOS) inhibitor: N G-nitro-l-arginine methyl ester (l-NAME) and an unselective neuronal NOS inhibitor: 7-nitroindazole (7-NI) inhibited the development of tolerance to the motor-impairing effects of FNZ in the rotarod and the chimney tests and (b) both a NO precursor: l-arginine and a selective inhibitor of phosphodiesterase 5 (PDE5): sildenafil did not affect the development of tolerance to FNZ-induced motor impairment in mice. Those findings provided behavioural evidence that NO could contribute an important role in the development of tolerance to FNZ in mice.

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“…Evidence indicates that the reinforcing properties of nicotine can be affected by several transmitter systems; among them the unorthodox nitric oxide (NO) neuromodulator seems to play a crucial role. In addition, a large body of evidence supports a direct DA/NO interaction under normal and pathological conditions such as Parkinson's disease (PD), schizophrenia, depression, and in drug addiction [21–25]. Hitherto, the role of NO in DA control is controversial [26].…”

Section: Introductionmentioning

confidence: 99%

“…On the contrary, evidence regarding the interrelationship between NO and drug of addiction such as nicotine is substantial and compelling. NO potentially contributes to nicotine central effects, such as reward, addiction, sensitization, and cognitive enhancement [25,27], although the exact neuronal mechanism of this modulation is still unclear, especially in the nigrostriatal system.…”

Section: Introductionmentioning

confidence: 99%

Critical role of Nitric Oxide on Nicotine‐Induced Hyperactivation of Dopaminergic Nigrostriatal System: Electrophysiological and Neurochemical evidence in Rats

Matteo¹,

Pierucci²,

Benigno

et al. 2010

CNS Neuroscience & Therapeutics

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Nicotine, the main psychoactive ingredient in tobacco, stimulates dopamine (DA) function, increasing DA neuronal activity and DA release. DA is involved in both motor control and in the rewarding and reinforcing effects of nicotine; however, the complete understanding of its molecular mechanisms is yet to be attained. Substantial evidence indicates that the reinforcing properties of drugs of abuse, including nicotine, can be affected by the nitric oxide (NO) system, which may act by modulating central dopaminergic function. In this study, using single cell recordings in vivo coupled with microiontophoresis and microdialysis in freely moving animals, the role of NO signaling on the hyperactivation elicited by nicotine of the nigrostriatal system was investigated in rats. Nicotine induced a dose-dependent increase of the firing activity of the substantia nigra pars compacta (SNc) DA neurons and DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in the striatum. Pharmacological manipulation of the NO system did not produce any change under basal condition in terms of neuronal discharge and DA release. In contrast, pretreatments with two NO synthase (NOS) inhibitors, N-ω-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) were both capable of blocking the nicotine-induced increase of SNc DA neuron activity and DA striatal levels. The effects of nicotine in L-NAME and 7-NI-pretreated rats were partially restored when rats were pretreated with the NO donor molsidomine. These results further support the evidence of an important role played by NO on modulation of dopaminergic function and drug addiction, thus revealing new pharmacological possibilities in the treatment of nicotine dependence and other DA dysfunctions.

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Nitric oxide and substance dependence

Cited by 109 publications

References 106 publications

Pharmacological characterization of the opioid inactive isomers (+)‐naltrexone and (+)‐naloxone as antagonists of toll‐like receptor 4

Pharmacological characterization of the opioid inactive isomers (+)‐naltrexone and (+)‐naloxone as antagonists of toll‐like receptor 4

The Importance of l-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice

Critical role of Nitric Oxide on Nicotine‐Induced Hyperactivation of Dopaminergic Nigrostriatal System: Electrophysiological and Neurochemical evidence in Rats

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