Morphine tolerance and dependence in the nociceptin receptor knockout mice

Mamiya, Takayoshi; Noda, Yukihiro; Ren, Xiuhai; Nagai, Taku; Takeshima, Hiroshi; Ukai, Makoto; Nabeshima, Toshitaka

doi:10.1007/s007020100012

Cited by 39 publications

(27 citation statements)

References 37 publications

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“…Interestingly the antinociceptive effect of morphine was reduced in NOP( À/ À ) compared to NOP(þ /þ) rats. This finding contrasts with that reported in mice where the analgesic effect of morphine was similar in NOP( þ/ þ) and NOP ( À/ À ) animals (Mamiya et al, 2001;Ueda et al, 1997). This might suggest an involvement of N/OFQergic signaling in the antinociceptive action of spinal morphine in rats but not in mice.…”

Section: Discussioncontrasting

confidence: 97%

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Micheli

Mannelli

Guerrini

et al. 2015

European Journal of Pharmacology

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a b s t r a c tSevere pain occurs in the context of many diseases and conditions and is a leading cause of disability. Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of the N/OFQ peptide (NOP) receptor. This peptidergic system controls pain transmission and in particular spinally administered N/OFQ has robust antinociceptive properties.The aim of this study was to investigate the spinal antinociceptive properties of NOP peptide agonists after acute and subchronic treatment in rats. Doses unable to alter motor coordination were selected. UFP-112 (full NOP agonist) and UFP-113 (partial NOP agonist) were administered intrathecally (i.t.) by spinal catheterization. Acute injection of UFP-112 induced antinociceptive response at lower dosages (0.03-1 nmol i.t.) compared to morphine and similar to N/OFQ. UFP-113 was effective in a 0.001-1 nmol i.t. dose range. The antinociceptive effects of NOP ligands were no longer evident in rats knockout for the NOP gene, while those of morphine were maintained. The continuous spinal infusion (by osmotic pumps) of 0.1 nmol/h UFP-112 and UFP-113 showed antinociceptive action comparable to 1-3 nmol/h morphine or N/OFQ. The antinociceptive effect of morphine progressively decreased and was no longer significant after 6 days of treatment. Similar results were obtained with N/OFQ, UFP-112, and UFP-113. The acute i.t. injection of morphine in animals tolerant to N/OFQ and UFP-112 evoked analgesic effects. Neither morphine nor N/OFQ induced antinociceptive effects in morphine-and UFP-113-tolerant rats. In conclusion this study highlights the analgesic efficacy and potency of UFP-112 and UFP-113 underlining the relevance of NOP system in analgesia.

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Section: Discussioncontrasting

confidence: 97%

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Micheli

Mannelli

Guerrini

et al. 2015

European Journal of Pharmacology

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“…As a means to understand the physiological role(s) of the endogenous N/OFQ-NOP receptor system, transgenic NOP Ϫ/Ϫ mice have been phenotyped in numerous biological and behavioral paradigms, including pain sensitivity (Bertorelli et al, 2002), locomotor activity (Nishi et al, 1997), morphine dependence and tolerance (Mamiya et al, 2001;Ueda, 2004), and antinociceptive response to morphine and -opioid peptides (Noda et al, 1999). Stress and anxiety (Gavioli et al, 2007), hyperalgesia and allodynia (Okuda-Ashitaka et al, 2006), auditory function (Nishi et al, 1997), learning and memory (Manabe et al, 1998), and depression (Gavioli et al, 2003(Gavioli et al, , 2004 have all also been examined in NOP Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 99%

Nociceptin/Orphanin FQ (N/OFQ)-Evoked Bradycardia, Hypotension, and Diuresis Are Absent in N/OFQ Peptide (NOP) Receptor Knockout Mice

Burmeister¹,

Ansonoff²,

Pintar³

et al. 2008

J Pharmacol Exp Ther

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Intracerebroventricular administration of the opioid-like peptide nociceptin/orphanin FQ (N/OFQ) produces bradycardia, hypotension, and diuresis in mice. We hypothesized that these responses are solely caused by selective activation of central N/OFQ peptide (NOP) receptors. To test this premise, we first examined whether i.c.v. N/OFQ produced dose-dependent diuretic and cardiovascular depressor responses in commercially available C57BL/6 mice. Next, using doses established in these studies, we examined the renal excretory and cardiovascular responses to i.c.v. N/OFQ in conscious transgenic NOP receptor knockout mice (NOP Ϫ/Ϫ ). In metabolic studies, i.c.v. N/OFQ, but not saline vehicle, dose-dependently increased urine output (V) in NOP ϩ/ϩ ; this response was significant at 3 nmol (N/OFQ, V ϭ 0.39 Ϯ 0.10 ml/2 h; saline, 0.08 Ϯ 0.05 ml/2 h). The N/OFQ-evoked diuresis was absent in littermate NOP Ϫ/Ϫ (N/OFQ, V ϭ 0.06 Ϯ 0.06 ml/2 h; saline, 0.03 Ϯ 0.03 ml/2 h).There were no significant changes in urinary sodium or potassium excretion or free water clearance in either group. In telemetry studies, i.c.v. N/OFQ dose dependently lowered heart rate (HR) and mean arterial pressure (MAP). At 3 nmol N/OFQ, both HR and MAP were reduced in NOP ϩ/ϩ (peak ⌬HR ϭ Ϫ217 Ϯ 31 bpm; peak ⌬MAP ϭ Ϫ47 Ϯ 7 mm Hg) compared with saline (peak ⌬HR ϭ Ϫ14 Ϯ 5 bpm; peak ⌬MAP ϭ 2 Ϯ 3 mm Hg). These N/OFQ-evoked bradycardic and hypotensive responses were absent in NOP Ϫ/Ϫ (peak ⌬HR ϭ Ϫ13 Ϯ 17 bpm; peak ⌬MAP ϭ Ϫ2 Ϯ 4 mm Hg, respectively). Basal 24-h cardiovascular and renal excretory function were not different between NOP Ϫ/Ϫ and NOP ϩ/ϩ mice. These results establish that the bradycardia, hypotension and diuresis produced by centrally administered N/OFQ are mediated by selective activation of NOP receptors.Nociceptin/orphanin FQ (N/OFQ) is an endogenous neuropeptide that selectively binds to and activates an opioidlike receptor called the N/OFQ peptide (NOP) receptor (previously called opioid receptor-like 1) (Meunier et al., 1995;Reinscheid et al., 1995). Although the N/OFQ-NOP system belongs to the opioid receptor family, classic opioid receptor agonists do not display appreciable binding affinity to the NOP receptor and vice versa (Lachowicz et al., 1995;Mollereau et al., 1999). Moreover, the N/OFQ-NOP system has pharmacological and physiological actions that are distinct from classic opioid receptor systems.We and other investigators have established that the central administration of N/OFQ produces novel changes in cardiovascular and renal excretory function. In conscious rats (Kapusta et al

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“…To develop morphine tolerance, mice received either morphine (10 mg/kg, s.c.) or saline twice daily for four days, at 09.00 and 16.00 h [25,26]. Mice were also treated with either obestatin or aCSF once a day at 09.45 h. On the fifth day, morphine was administrated only in the morning at 09.00 h. Obestatin treatment was the same as in the previous days.…”

Section: The Effect Of Obestatin On Analgesic Tolerance To Morphinementioning

confidence: 99%

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Lipták

Dochnal

Csabafi

et al. 2013

Regulatory Peptides

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Obestatin is a 23-amino acid gut-derived neuropeptide, encoded by the same gene with ghrelin. The goal of this study was to examine the effects of obestatin on the acute and chronic analgesic actions of morphine and on mild morphine withdrawal. Open-field (OF) and elevated plus maze (EPM) tests were used to assess mild morphine withdrawal-induced behavior changes and the heat-radiant tail-flick assay was used to investigate analgesic actions of morphine. CFLP male mice were treated twice a day with graded doses of morphine in EPM and OF experiments and once a day in tail-flick studies. Obestatin (1.5 μg/2 μl) was administrated once a day in all experiments. Furthermore, 0.2 mg/kg naloxone or saline was administered after the final injection of morphine at a dose of 20 mg/kg in EPM and OF. These behavioral parameters were monitored in the OF: the percentage of center ambulation time and distance; whereas in the EPM: the time spent in open arms and the entries into open arms compared to the total time (%OAT) and entries (%OAE). In the OF, obestatin significantly decreased the percentage of time spent in the center in mice undergoing naloxone-precipitated mild morphine withdrawal. EPM results were similar to open field, but obestatin had no significant effect on parameters mentioned above. Besides, obestatin maintained the analgesic effect of morphine 90 and 120 min after morphine injection in mice treated with morphine receiving obestatin compared to mice treated with morphine. In tolerance studies, obestatin diminished the analgesic tolerance to morphine on the 5th day. In this study we confirmed that obestatin reversed the effect of mild morphine withdrawal and enhances the analgesic effect of morphine. These data suggest that obestatin may have a role in opioid-induced analgesia and in behavioral responses induced by opioid withdrawal.

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Morphine tolerance and dependence in the nociceptin receptor knockout mice

Cited by 39 publications

References 37 publications

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Nociceptin/Orphanin FQ (N/OFQ)-Evoked Bradycardia, Hypotension, and Diuresis Are Absent in N/OFQ Peptide (NOP) Receptor Knockout Mice

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

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