Local μ-Opioid Receptor Antagonism Blunts Evoked Phasic Dopamine Release in the Nucleus Accumbens of Rats

ACS Chem Neurosci. 2019 Apr 17;10(4):1935-1940. doi: 10.1021/acschemneuro.8b00437. Epub 2018 Nov 6.

Abstract

μ-opioid receptors (MORs) in the nucleus accumbens (NAc) can regulate reward-related behaviors that are dependent on mesolimbic dopamine, but the precise mechanism of this MOR regulation is unknown. We hypothesized that MORs within the NAc core regulate dopamine release. Specifically, we infused the MOR antagonist CTAP (d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2) into the NAc core while dopamine release was evoked by electrical stimulation of the ventral tegmental area and measured by fast-scan cyclic voltammetry. We report that CTAP dose-dependently inhibited evoked dopamine release, with full blockade achieved with the 8 μg infusion. In contrast, evoked dopamine release increased after nomifensine infusion and was unchanged after vehicle infusion. These findings demonstrate profound local control of dopamine release by MORs within the NAc core, which has implications for regulation of reward processing.

Keywords: accumbens; dopamine; electrochemistry; local infusion; phasic; μ-opioid receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dose-Response Relationship, Drug
  • Infusions, Intraventricular
  • Male
  • Narcotic Antagonists / administration & dosage*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Peptide Fragments / administration & dosage*
  • Rats
  • Rats, Long-Evans
  • Receptors, Opioid, mu / antagonists & inhibitors*
  • Receptors, Opioid, mu / metabolism*
  • Somatostatin / administration & dosage*

Substances

  • CTAP octapeptide
  • Dopamine Uptake Inhibitors
  • Narcotic Antagonists
  • Peptide Fragments
  • Receptors, Opioid, mu
  • Somatostatin
  • Dopamine