liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Pharmacological blockage of NOP receptors decreases ventral tegmental area dopamine neuronal activity through GABAB receptor-mediated mechanism
Univ Camerino, Italy.
Univ Camerino, Italy.
Univ Florence, Italy.
Univ Camerino, Italy.
Show others and affiliations
2024 (English)In: Neuropharmacology, ISSN 0028-3908, E-ISSN 1873-7064, Vol. 248, article id 109866Article in journal (Refereed) Published
Abstract [en]

The Nociceptin/Orphanin FQ (N/OFQ) peptide and its receptor NOP are highly expressed within several regions of the mesolimbic system, including the ventral tegmental area (VTA). Evidence indicates that the N/OFQ-NOP receptor system is involved in reward processing and historically it has been proposed that activation of NOP receptors attenuates the motivation for substances of abuse. However, recent findings demonstrated that drug self -administration and relapse to drug -seeking are also attenuated after administration of NOP receptor antagonists. Here, to shed light on the mechanisms through which NOP receptor blockers modulate these processes, we utilized ex vivo patch -clamp recordings to investigate the effect of the selective NOP receptor antagonist LY2817412 on VTA dopaminergic (DA) function in male rats. Results showed that, similar to the endogenous NOP receptor agonist N/OFQ, LY2817412 reduced the spontaneous basal firing discharge of VTA DA neurons. Consistently, we found that NOP receptors are expressed both in VTA DA and GABA cells and that LY2817412 slice perfusion increased GABA release onto VTA DA cells. Finally, in the attempt to dissect the role of postsynaptic and presynaptic NOP receptors, we tested the effect of N/OFQ and LY2817412 in the presence of GABA receptors blockers. Results showed that the effect of LY2817412 was abolished following pretreatment with GABABR, but not GABAAR, blockers. Conversely, inhibition of DA neuronal activity by N/OFQ was unaffected by blockade of GABA receptors. Altogether, these results suggest that both NOP receptor agonists and antagonists can decrease VTA DA neuronal activity, but through distinct mechanisms of action. The effect of NOP receptor antagonists occurs through a GABABR-mediated mechanism while NOP receptor agonists seem to act via a direct effect on VTA DA neurons.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD , 2024. Vol. 248, article id 109866
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-202529DOI: 10.1016/j.neuropharm.2024.109866ISI: 001196905700001PubMedID: 38364970OAI: oai:DiVA.org:liu-202529DiVA, id: diva2:1851970
Note

Funding Agencies|National Institute on Alcohol Abuse and Alcoholism [AA014351, AA017447]

Available from: 2024-04-16 Created: 2024-04-16 Last updated: 2024-04-16

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Domi, EsiXu, LiBarbier, EstelleHeilig, Markus
By organisation
Center for Social and Affective NeuroscienceFaculty of Medicine and Health SciencesPsykiatriska kliniken i Linköping
In the same journal
Neuropharmacology
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 51 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf