Neuropeptide FF (NPFF) reduces the expression of cocaine-induced conditioned place preference and cocaine-induced sensitization in animals

Kotlińska, Jolanta; Pachuta, Agnieszka; Silberring, Jerzy

doi:10.1016/j.peptides.2008.01.008

Cited by 22 publications

(13 citation statements)

References 48 publications

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“…21 Moreover, it was suggested that NPFF is involved in the mechanism of expression of sensitization to cocaine hyperlocomotion, although this effect could be nonspecific. 22 Consistent with these observations, there is evidence that NPFF binding sites are abundant in the ventral tegmental area (VTA), while NPFF-like immunoreactivity was detected in the nucleus accumbens (NAc), two brain regions belonging to the mesolimbic dopamine DA projections, which are known to be involved in drug addiction. 23 Together, these findings suggest that the NPFF system is a viable target for the treatment of drug addiction.…”

Section: ■ Introductionmentioning

confidence: 76%

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Discovery of Novel Proline-Based Neuropeptide FF Receptor Antagonists

Nguyễn

Decker

Langston

et al. 2017

ACS Chem. Neurosci.

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The neuropeptide FF (NPFF) system has been implicated in a number of physiological processes including modulating the pharmacological activity of opioid analgesics and several other classes of drugs of abuse. In this study, we report the discovery of a novel proline scaffold with antagonistic activity at the NPFF receptors through a high throughput screening campaign using a functional calcium mobilization assay. Focused structure-activity relationship studies on the initial hit 1 have resulted in several analogs with calcium mobilization potencies in the submicromolar range and modest selectivity for the NPFF1 receptor. Affinities and potencies of these compounds were confirmed in radioligand binding and functional cAMP assays. Two compounds, 16 and 33, had good solubility and blood-brain barrier permeability that fall within the range of CNS permeant candidates without the liability of being a P-glycoprotein substrate. Finally, both compounds reversed fentanyl-induced hyperalgesia in rats when administered intraperitoneally. Together, these results point to the potential of these proline analogs as promising NPFF receptor antagonists.

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Section: ■ Introductionmentioning

confidence: 76%

“…The cyclohexyl analog 21 (NPFF1 K e = 1.12 μM) is slightly more potent than the more hydrophilic morpholinyl counterpart 20 (NPFF1 K e = 1.96 μM). The flexible N,N-diethylaminoethyl side chain (22) was inactive at both receptors. These results suggest that introduction of a heteroatom is not well tolerated in this region.…”

Section: ■ Introductionmentioning

confidence: 95%

Discovery of Novel Proline-Based Neuropeptide FF Receptor Antagonists

Nguyễn

Decker

Langston

et al. 2017

ACS Chem. Neurosci.

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“…Neuropeptides have been identified to play important roles in modulating the rewarding value of abused drugs, as well as drug addiction 33 40 41 . Peng et al .…”

Section: Discussionmentioning

confidence: 99%

mTOR signalling in the nucleus accumbens shell is critical for augmented effect of TFF3 on behavioural response to cocaine

Luo

Han

Shao

et al. 2016

Sci Rep

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Neuropeptides play important roles in modulating the rewarding value of abused drugs. Trefoil factor 3 (TFF3) was recently reported to modulate withdrawal syndrome of morphine, but the effects of TFF3 on the cocaine-induced behavioral changes are still elusive. In the present study, cocaine-induced hyperlocomotion and conditioned place preference (CPP) rat paradigms were provided to investigate the role of TFF3 in the reward response to cocaine. High-performance liquid chromatography (HPLC) analysis was used to analyse the dopamine concentration. The results showed that systemic TFF3 administration (0.1 mg/kg i.p.) significantly augmented cocaine- induced hyperlocomotion and CPP formation, without any effects on locomotor activity and aversive or rewarding effects per se. TFF3 significantly augmented the increment of the dopamine concentration in the NAc and the activity of the mTOR signalling pathway induced by acute cocaine exposure (10 mg/kg, i.p.) in the NAc shell, but not the core. The Intra-NAc shell infusion of rapamycin blocked TFF3-induced hyperactivity in cocaine-treatment rats. These findings indicated that TFF3 could potentiate behavioural response to cocaine, which may be associated with regulating dopamine concentration. Furthermore, the findings indicated that mTOR signalling pathway in the NAc shell is important for TFF3-induced enhancement on the cocaine-induced behavioral changes.

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“…In line with this, i.c.v. injections of NPFF have been reported to reduce the expression of cocaine‐induced CPP and sensitization to cocaine hyperlocomotor effects in rats, suggesting that the NPFF system could also be activated following chronic administration of other addictive drugs (Kotlinska et al ., 2008).…”

Section: Discussionmentioning

confidence: 99%

Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments

Elhabazi

Mollereau

et al. 2011

British J Pharmacology

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BACKGROUND AND PURPOSEOpiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACHThe effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTSRF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONSThe NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. AbbreviationsCPP, conditioned place preference; HMA, horizontal motor activity; NPFF, neuropeptide FF; OIH, opioid-induced hyperalgesia; VMA, vertical motor activity BJP British Journal of Pharmacology

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Neuropeptide FF (NPFF) reduces the expression of cocaine-induced conditioned place preference and cocaine-induced sensitization in animals

Cited by 22 publications

References 48 publications

Discovery of Novel Proline-Based Neuropeptide FF Receptor Antagonists

Discovery of Novel Proline-Based Neuropeptide FF Receptor Antagonists

mTOR signalling in the nucleus accumbens shell is critical for augmented effect of TFF3 on behavioural response to cocaine

Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments

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