Neuropeptide FF (NPFF) reduces the expression of morphine- but not of ethanol-induced conditioned place preference in rats

Kotlińska, Jolanta; Pachuta, Agnieszka; Dyląg, Tomasz; Silberring, Jerzy

doi:10.1016/j.peptides.2007.08.006

Cited by 46 publications

(25 citation statements)

References 68 publications

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“…Besides routes of alcohol administration and genetic variables of animals used, it has been suggested that varying timing of ethanol administration and ethanol-pairing cues can induce both CPP and place aversion in the same animal (Cunningham et al, 2002, Green and Grahame, 2008), underscoring the effect of experimental conditions on the outcome of alcohol conditioning. In fact, there are numerous previous reports of ethanol-induced CPP in rats with either biased or unbiased procedures (Bozarth, 1990, Bienkowski et al, 1996, Biala and Kotlinska, 1999, Ciccocioppo et al, 2003, Cole et al, 2003, Kotlinska et al, 2007, Walker and Ettenberg, 2007, Peana et al, 2008). Under our experimental conditions, both ethanol and morphine, a strong rewarding opioid, induce similar CPP, supporting the involvement of a rewarding effect of alcohol in the CPP behavior in rats (Zhu et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Ethanol-induced delta-opioid receptor modulation of glutamate synaptic transmission and conditioned place preference in central amygdala

2009

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Alcoholism involves compulsive behaviors of alcohol drinking, which is thought to be related at least initially to the rewarding effect of alcohol. It has been shown that mu-opioid receptors play an essential role in drug reward and dependence for many drugs of abuse including alcohol, but the function of delta-opioid receptors (DOR) in drug reward remains largely unknown at present. Previous animal studies using systemic approaches with DOR antagonists or DOR knockout animals have yielded inconsistent results, showing a decrease, an increase or no change in alcohol consumption and behaviors of alcohol reward after DOR inhibition or deletion. In the present study, we used ethanol-conditioned rats to investigate adaptive DOR function in neurons of the central nucleus of the amygdala (CeA), a key brain site for alcohol reward and addiction. We found that functional DOR was absent in glutamate synapses of CeA neurons from control rats, but it emerged and inhibited glutamate synaptic currents in CeA neurons from rats displaying ethanol-induced behavior of conditioned place preference (CPP). Analysis of paired-pulse ratios and miniature glutamate synaptic currents revealed that the recruited DOR was present on glutamatergic presynaptic terminals. Similar induction of functional DOR was also found on GABA synapses. Furthermore, microinjection of a DOR antagonist into the CeA reversed ethanol-induced CPP behavior in rats in vivo. These results suggest that repeated alcohol exposure recruits new functional DOR on CeA glutamate and GABA synapses, which may be involved in the expression or maintenance of ethanol-induced CPP behavior.

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Section: Discussionmentioning

confidence: 99%

Ethanol-induced delta-opioid receptor modulation of glutamate synaptic transmission and conditioned place preference in central amygdala

2009

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“…In addition, the NPFF receptor antagonist RF9 significantly blocked opioid tolerance and physical dependence (Simonin et al , ). It is notable that NPFF was found to inhibit the acquisition and expression of morphine‐induced conditioned place preference (CPP) and the acquisition and the expression of endomorphin‐2‐induced conditioned place aversion (Marchand et al , ; Kotlinska et al , ; Han et al , ). Therefore, it seems that activation of NPFF receptors can reduce opioid‐induced reward.…”

Section: Introductionmentioning

confidence: 99%

BN‐9, a chimeric peptide with mixed opioid and neuropeptide FF receptor agonistic properties, produces nontolerance‐forming antinociception in mice

Han

Wang

et al. 2016

British J Pharmacology

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BACKGROUND AND PURPOSENeuropeptide FF (NPFF) behaves as an endogenous opioid-modulating peptide. In the present study, the opioid and NPFF pharmacophore-containing chimeric peptide BN-9 was synthesized and pharmacologically characterized. EXPERIMENTAL APPROACHAgonist activities of BN-9 at opioid and NPFF receptors were characterized in in vitro cAMP assays. Antinociceptive activities of BN-9 were evaluated in the mouse tail-flick and formalin tests. Furthermore, its side effects were investigated in rotarod, antinociceptive tolerance, reward and gastrointestinal transit tests. KEY RESULTSBN-9 acted as a novel multifunctional agonist at μ, δ, κ, NPFF1 and NPFF2 receptors in cAMP assays. In the tail-flick test, BN-9 produced dose-related antinociception and was approximately equipotent to morphine; this antinociception was blocked by μ and κ receptor antagonists, but not by the δ receptor antagonist. In the formalin test, supraspinal administration of BN-9 produced significant analgesia. Notably, repeated administration of BN-9 produced analgesia without loss of potency over 8 days. In contrast, repeated i.c.v. co-administration of BN-9 with the NPFF receptor antagonist RF9 produced significant antinociceptive tolerance. Furthermore, i.c.v. BN-9 induced conditioned place preference. When given by the same routes, BN-9 had a more than eightfold higher ED 50 value for gastrointestinal transit inhibition compared with the ED 50 values for antinociception. CONCLUSIONS AND IMPLICATIONSBN-9 produced a robust, nontolerance-forming analgesia with limited inhibition of gastrointestinal transit. As BN-9 is able to activate both opioid and NPFF systems, this provides an interesting approach for the development of novel analgesics with minimal side effects.

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“…NPFF is sometimes considered an anti-opiate peptide since it antagonizes various acute effects of opiate drugs [5][6][7]. Conversely, antibodies and antagonists to NPFF administered i.c.v.…”

Section: Introductionmentioning

confidence: 99%

Reversal of morphine tolerance by a compound with NPFF receptor subtype-selective actions

Malin

Henceroth

Izygon

et al. 2015

Neuroscience Letters

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Neuropeptide FF (NPFF) modulates opiate actions. It has pro-nociceptive effects, primarily through the NPFF receptor 1 subtype, and anti-nociceptive effects, primarily through the NPFFR2 subtype. AC-263093 is a small l, organic, systemically active molecule that was previously shown to functionally activate NPFFR2, but not NPFFR1. It was hypothesized that AC-263093 would attenuate morphine tolerance. Rats were tested for radiant heat tail-flick latency before and after 5 mg/kg morphine sulfate s.c. They were then rendered morphine-tolerant by continuous subcutaneous infusion of 17.52 mg/kg/day morphine sulfate. On the seventh day of infusion, they were retested for analgesia 10 and 20 min after 5mg/kg morphine sulfate s.c. Tolerance was indicated by reduction of morphine analgesia from the pre-infusion test. Fifty minutes prior to morphine challenge, rats received either 10 mg/kg i.p. AC-263093 or injection vehicle alone. AC-2623093-treated rats had far smaller tolerance scores than control rats. This drug effect was significant, p = 0.015. The same dose of AC-263093 had almost no analgesic effect in non-tolerant, saline-infused rats. In vitro experiments revealed that AC-263093 had equal affinity for NPFFR1 and NPFFR2, and functionally inactivated NPFFR1, in addition to its previously shown ability to activate NPFFR2. Thus, altering the balance between activation of NPFF receptor subtypes may provide one approach to reversing opiate tolerance.

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Neuropeptide FF (NPFF) reduces the expression of morphine- but not of ethanol-induced conditioned place preference in rats

Cited by 46 publications

References 68 publications

Ethanol-induced delta-opioid receptor modulation of glutamate synaptic transmission and conditioned place preference in central amygdala

Ethanol-induced delta-opioid receptor modulation of glutamate synaptic transmission and conditioned place preference in central amygdala

BN‐9, a chimeric peptide with mixed opioid and neuropeptide FF receptor agonistic properties, produces nontolerance‐forming antinociception in mice

Reversal of morphine tolerance by a compound with NPFF receptor subtype-selective actions

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