Genetic Deletion or Pharmacological Blockade of Nociceptin/Orphanin FQ Receptors in the Ventral Tegmental Area Attenuates Nicotine‐Motivated Behaviour

2021 ◽  
Author(s):  
Ana Domi ◽  
Veronica Lunerti ◽  
Michele Petrella ◽  
Esi Domi ◽  
Anna Maria Borruto ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Orphanin Fq ◽  
Pharmacological Blockade ◽  
Genetic Deletion ◽  
Ventral Tegmental

scholarly journals Differential modulation of ventral tegmental area circuits by the nociceptin/orphanin FQ system

2019 ◽  
Author(s):  
Joseph R. Driscoll ◽  
Tanya L. Wallace ◽  
Kasra A. Mansourian ◽  
William J. Martin ◽  
Elyssa B. Margolis
Keyword(s):  
Ventral Tegmental Area ◽  
Reward Processing ◽  
Anterior Cingulate ◽  
Substantia Nigra Pars Compacta ◽  
Orphanin Fq ◽  
Whole Cell ◽  
First Response ◽  
Outward Currents ◽  
Inward Currents ◽  
Ventral Tegmental

AbstractThe neuropeptide nociceptin/orphanin FQ (N/OFQ) can be released by stressors and is associated with disorders of emotion regulation and reward processing. N/OFQ and its receptor, NOP, are enriched in dopaminergic pathways, and intra-ventricular agonist delivery decreases dopamine levels in the dorsal striatum, nucleus accumbens (NAc), and ventral tegmental area (VTA). We used whole cell electrophysiology in acute rat midbrain slices to investigate synaptic actions of N/OFQ. N/OFQ was primarily inhibitory, causing outward currents in both immunocytochemically identified dopaminergic (tyrosine hydroxylase positive (TH(+)) and non-dopaminergic (TH(−)) VTA neurons (effect at 1 μM: 20 ± 4 pA). Surprisingly, this effect was mediated by augmentation of postsynaptic GABAAR currents, unlike the substantia nigra pars compacta (SNc), where the N/OFQ induced outward currents were K+ channel dependent. A smaller population, 19% of all VTA neurons, responded to low concentrations N/OFQ with inward currents (10 nM: −11 ± 2 pA). Following 100 nM N/OFQ, the response to a second N/OFQ application was markedly diminished in VTA neurons (14 ± 10% of first response), but not in SNc neurons (90 ± 20% of first response). N/OFQ generated outward currents in medial prefrontal cortex (mPFC)-projecting VTA neurons, but inward currents in a subset of posterior anterior cingulate cortex-projecting VTA neurons. While N/OFQ inhibited NAc-projecting VTA cell bodies, it had little effect on electrically or optogenetically evoked terminal dopamine release in the NAc measured ex vivo with fast scan cyclic voltammetry. These results extend our understanding of the N/OFQ system in brainstem circuits implicated in many neurobehavioral disorders.Significance statementThe neuropeptide nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are engaged under conditions of stress and are associated with reward processing disorders. Both peptide and receptor are highly enriched in ventral tegmental area (VTA) pathways underlying motivation and reward. Using whole cell electrophysiology in rat midbrain slices we found: 1) NOPs are functional on both dopaminergic and non-dopaminergic VTA neurons; 2) N/OFQ differentially regulates VTA neurons based on neuroanatomical projection target; and 3) repeated application of N/OFQ produces evidence of receptor desensitization in the VTA but not the SNc. These results reveal candidate mechanisms by which the NOP system regulates motivation and emotion.

scholarly journals Actions of orphanin FQ/nociceptin on rat ventral tegmental area neurons in vitro

2002 ◽  
Vol 136 (7) ◽  
pp. 1065-1071 ◽  
Author(s):  
Fang Zheng ◽  
David K Grandy ◽  
Steven W Johnson
Keyword(s):  
Ventral Tegmental Area ◽  
Orphanin Fq ◽  
Ventral Tegmental

scholarly journals Differential Modulation of Ventral Tegmental Area Circuits by the Nociceptin/Orphanin FQ System

eNeuro ◽  
2020 ◽  
Vol 7 (5) ◽  
pp. ENEURO.0376-19.2020
Author(s):  
Joseph R. Driscoll ◽  
Tanya L. Wallace ◽  
Kasra A. Mansourian ◽  
William J. Martin ◽  
Elyssa B. Margolis
Keyword(s):  
Ventral Tegmental Area ◽  
Differential Modulation ◽  
Orphanin Fq ◽  
Ventral Tegmental
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