Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location

Christopher P. Ford, Gregory P. Mark, John T. Williams

Research output: Contribution to journalArticlepeer-review

255 Scopus citations


The mesolimbic dopamine system, which mediates the rewarding properties of nearly all drugs of abuse, originates in the ventral tegmental area (VTA) and sends major projections to both the nucleus accumbens (NAc) and the basolateral amygdala (BLA). To address whether differences occur between neurons that project to these separate areas, retrograde microspheres were injected to either the BLA or the NAc of DBA/2J mice. Whole-cell recordings were made from labeled VTA dopamine neurons. We found that identified neurons that projected to the BLA and NAc originated within different quadrants of the VTA with neither group exhibiting large-amplitude h-currents. Neurons that projected to the NAc exhibited a greater outward current in response to the κ-opioid agonist (5α,7α,8α)-(+)-N-methyl-N-[7-(pyrrolidinyl)-1-oxaspiro [4,5]dec-8-yl]-benzeneacetamide (U69593; 200 nM), whereas neurons that projected to the BLA exhibited greater inhibition to the μ/δ opioid agonist [Met5] enkephalin (ME; 3 μM). In addition, we found that the presynaptic inhibition of GABAergic transmission at both GABAA and GABAB receptors was differentially regulated by U69593 between the two groups. When dopamine IPSCs were examined, U69593 caused a greater inhibition in NAc- than BLA-projecting neurons. ME had no effect on either. Finally, the regulation of extracellular dopamine by dopamine uptake transporters was equal across the VTA. These results suggest that opioids differentially inhibit mesolimbic neurons depending on their target projections. Identifying the properties of projecting mesolimbic VTA dopamine neurons is crucial to understanding the action of drugs of abuse.

Original languageEnglish (US)
Pages (from-to)2788-2797
Number of pages10
JournalJournal of Neuroscience
Issue number10
StatePublished - Mar 8 2006


  • Morphine
  • Retrograde labeling
  • Ventral tegmental area
  • Withdrawal
  • κ-opioid
  • μ-opioid

ASJC Scopus subject areas

  • Neuroscience(all)


Dive into the research topics of 'Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location'. Together they form a unique fingerprint.

Cite this