Orphanin FQ inhibits synaptic transmission and long‐term potentiation in rat hippocampus

Yu, Tzu‐Ping; Fein, Jeffrey; Phan, Tien; Evans, Christopher J.; Xie, Cui‐Wei

doi:10.1002/(sici)1098-1063(1997)7:1<88::aid-hipo9>3.3.co;2-5

Cited by 18 publications

(30 citation statements)

References 17 publications

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“…In contrast to the report of Yu et al (1997), OFQ/N application had no effect on ®eld EPSP slopes and moreover, we observed a similar effect of OFQ/N in rat hippocampal slices, i.e., inhibition of LTP induction without effect on ®eld EPSP slope. However, in agreement with Yu et al (1997), we observed a depression of evoked CA1 population spikes following application of OFQ/N (data not shown). Thus, it is likely that OFQ/N exerts a postsynaptic inhibitory action in CA1 pyramidal neurons, which could be mediated by activation of potassium conductances (Ikeda et al, 1997;Madamba et al, 1999) or inhibition of calcium currents (Kno¯ach et al, 1996).…”

Section: Discussioncontrasting

confidence: 97%

A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory

Higgins

Kew

Richards

et al. 2002

Eur J of Neuroscience

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Using a combination of the selective opioid receptor-like1 (ORL1) receptor agonist, Ro 64-6198, and orphanin FQ/nociceptin (OFQ/N) peptide knockout (KO) mice, the influence of OFQ/N on cognition has been studied in the rodent. In wild type, C57BL/6J mice, Ro 64-6198 (0.3-1 mg/kg i.p.) impaired the acquisition of spatial learning in the Morris water maze, although a mild neurological impairment was evident which complicated precise interpretation. In Lister hooded rats, Ro 64-6198 (6 mg/kg i.p.) produced delay dependent impairments in rats performing either a delayed matching or a delayed nonmatching to position task with only a modest (< 20%) effect on omissions - an effect consistent with a short-term memory impairment. Electrophysiological studies demonstrated an inhibitory effect of OFQ/N on LTP recorded from the CA1 region of wild type mice, but not in ORL1 receptor knockout mice. In contrast to the ORL1 agonist, mice deficient in the OFQ/N peptide showed some evidence of improved spatial learning, fear conditioning and passive avoidance retention. However, CA1 LTP was similar between OFQ/N peptide KO mice and wild type controls. Subsequent receptor radioautography studies demonstrated the presence of ORL1 receptors within various regions of the medial temporal lobe system: i.e. CA1, dentate gyrus molecular layer, subiculum, perirhinal cortex. Taken together, these results suggest a bi-directional effect of OFQ/N containing systems on aspects of cognitive behaviour, particularly those elements associated with hippocampal function. This is consistent with a likely modulatory role of OFQ/N on hippocampal and associated cortical circuitry.

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Section: Discussioncontrasting

confidence: 97%

A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory

Higgins

Kew

Richards

et al. 2002

Eur J of Neuroscience

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“…Second, unlike OFQ/N, DAMGO is a stable analogue and peptidase inhibitors were not used in this study. Third, and perhaps most important, the receptor inactive analogue des-Phe 1 -OFQ/N (Matthes et al, 1996;Yu et al, 1997) did not decrease DA levels at the same 1 mM concentration. As des-Phe 1 -OFQ/N differs in structure from OFQ/N by one amino acid, the rate of recovery of this analogue is likely to be very similar and thus the dose of des-Phe 1 -OFQ/N is directly comparable.…”

Section: Discussionmentioning

confidence: 98%

Orphanin FQ/Nociceptin Modulation of Mesolimbic Dopamine Transmission Determined by Microdialysis

Murphy¹,

Maidment²

1999

Journal of Neurochemistry

147

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Orphanin FQ has been reported to suppress extracellular dopamine levels in the nucleus accumbens after intracerebroventricular administration. This study sought to provide evidence for an intra-ventral tegmental site of action for this effect using a dual-probe microdialysis experimental design. Orphanin FQ was applied to the ventral tegmental area of anesthetized rats by reverse dialysis while extracellular dopamine was sampled with a second dialysis probe in the nucleus accumbens. Orphanin FQ at a probe concentration of 1 mM (but not at 0.1 mM) significantly reduced nucleus accumbens dialysate dopamine levels. The receptor-inactive analogue, desPhe 1 -orphanin FQ (1 mM), produced a small but significant increase in nucleus accumbens dialysate dopamine levels. Simultaneous measurement of ventral tegmental area dialysate amino acid content revealed significant increases in both GABA and glutamate during infusion of orphanin FQ (1 mM). To determine if increased GABA overflow mediates the action of orphanin FQ on mesolimbic neurons, orphanin FQ (10 nmol) was microinjected directly into the ventral tegmental area in the presence or absence of the GABA A receptor antagonist, bicuculline (1 nmol). Bicuculline transiently blocked the suppressive action of orphanin FQ on accumbens dialysate dopamine levels. These data indicate that orphanin FQ decreases dopamine transmission in the nucleus accumbens by inhibiting dopamine neuronal activity in the ventral tegmental area through a mechanism that may involve an increased overflow of GABA. Key Words: Dopamine -Mesolimbic-Microdialysis-Orphanin FQNociceptin-GABA.

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“…Several OFQ fragments with high affinity binding to the ORL1 receptor also have been identified (Dooley et al, 1997). Binding of OFQ to the ORL1 receptor has been shown to stimulate ORL1-induced Ca 2ϩ and K ϩ conductance changes (Conner et al, 1996(Conner et al, , 1997Knoflach et al, 1996;Nicol et al, 1996;Vaughan and Christie, 1996;Abdulla and Smith, 1997; Vaughan et al, 1997;Yu et al, 1997;Wagner et al, 1998), protein kinase C activation (Lou et al, 1997), and to effect the function of other neurotransmitter systems (Faber et al, 1996;Giuliani and Maggi, 1996;Murphy et al, 1996;Wang et al, 1996;Gintzler et al 1997;Liebel et al, 1997;Inoue et al, 1998;Konya et al, 1998). Intraven-tricular injection of OFQ fails to produce cross-tolerance with morphine or conditioned place preference (Devine et al, 1996a), but it has been implicated in various modulatory effects of allodynia (Hara et al, 1997;Minami et al, 1997) and nociception (Grisel et al, 1996;Mogil et al, 1996a,b;Rossi et al, 1996 Xu et al, 1996;Dawson-Basoa and Gintzler, 1997;Heinricher et al, 1997;King et al, 1997;Liebel et al, 1997;Morgan et al 1997;Nishi et al, 1997;Tian et al, 1997a,b;Yamamoto et al, 1997;Zhu et al, 1997), enticing many to refer to this molecule as nociceptin.…”

Section: Indexing Terms: Receptor Autoradiography; In Situ Hybridizatmentioning

confidence: 99%

“…The role of orphanin in the hippocampus is presently not clear. However, orphanin has been reported to reversibly inhibit voltage-gated calcium channels in pyramidal neurons from area CA1 and CA3 (Knoflach et al, 1996) and to inhibit synaptic transmission and long-term potentiation in area CA1 of Ammon's horn and the dentate gyrus (Yu et al, 1997). The latter effect is thought to be presynaptic in nature.…”

Section: Orphanin Fq and Orl1 Receptor Circuitrymentioning

confidence: 99%

Opioid receptor‐like (ORL1) receptor distribution in the rat central nervous system: Comparison of ORL1 receptor mRNA expression with 125I‐[14Tyr]‐orphanin FQ binding

Neal

Mansour²,

Reinscheid

et al. 1999

J. Comp. Neurol.

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The recently discovered neuropeptide orphanin FQ (OFQ), and its opioid receptor-like (ORL1) receptor, exhibit structural features suggestive of the micro, kappa, and delta opioid systems. The anatomic distribution of OFQ immunoreactivity and mRNA expression has been reported recently. In the present analysis, we compare the distribution of orphanin receptor mRNA expression with that of orphanin FQ binding at the ORL1 receptor in the adult rat central nervous system (CNS). By using in vitro receptor autoradiography with (125)I-[(14)Tyr]-OFQ as the radioligand, orphanin receptor binding was analyzed throughout the rat CNS. Orphanin binding sites were densest in several cortical regions, the anterior olfactory nucleus, lateral septum, ventral forebrain, several hypothalamic nuclei, hippocampal formation, basolateral and medial amygdala, central gray, pontine nuclei, interpeduncular nucleus, substantia nigra, raphe complex, locus coeruleus, vestibular nuclear complex, and the spinal cord. By using in situ hybridization, cells expressing ORL1 mRNA were most numerous throughout multiple cortical regions, the anterior olfactory nucleus, lateral septum, endopiriform nucleus, ventral forebrain, multiple hypothalamic nuclei, nucleus of the lateral olfactory tract, medial amygdala, hippocampal formation, substantia nigra, ventral tegmental area, central gray, raphe complex, locus coeruleus, multiple brainstem motor nuclei, inferior olive, deep cerebellar nuclei, vestibular nuclear complex, nucleus of the solitary tract, reticular formation, dorsal root ganglia, and spinal cord. The diffuse distribution of ORL1 mRNA and binding supports an extensive role for orphanin FQ in a multitude of CNS functions, including motor and balance control, reinforcement and reward, nociception, the stress response, sexual behavior, aggression, and autonomic control of physiologic processes.

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Orphanin FQ inhibits synaptic transmission and long‐term potentiation in rat hippocampus

Cited by 18 publications

References 17 publications

A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory

A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory

Orphanin FQ/Nociceptin Modulation of Mesolimbic Dopamine Transmission Determined by Microdialysis

Opioid receptor‐like (ORL1) receptor distribution in the rat central nervous system: Comparison of ORL1 receptor mRNA expression with 125I‐[14Tyr]‐orphanin FQ binding

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