Properties and Opioid Inhibition of Mesolimbic Dopamine Neurons Vary according to Target Location

• Published in: The Journal of neuroscience 2006-03, Vol.26 (10), p.2788-2797
• Main Authors: Ford, Christopher P, Mark, Gregory P, Williams, John T
• Format: Article
• Language: English
• Subjects: Amygdala - cytology; Amygdala - metabolism; Analgesics - pharmacology; Animals; Bicuculline - analogs & derivatives; Bicuculline - pharmacology; Biotin - analogs & derivatives; Biotin - metabolism; Cell Count - methods; Dopamine - metabolism; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation - methods; Female; GABA Antagonists - pharmacology; Immunohistochemistry - methods; In Vitro Techniques; Limbic System - cytology; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Mice; Mice, Inbred DBA; Microinjections - methods; Molecular Sequence Data; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Narcotics - pharmacology; Neural Inhibition - drug effects; Neural Pathways - drug effects; Neural Pathways - physiology; Neurons - classification; Neurons - drug effects; Neurons - metabolism; Nucleus Accumbens - cytology; Nucleus Accumbens - metabolism; Patch-Clamp Techniques - methods; Reaction Time - drug effects; Reaction Time - physiology; Reaction Time - radiation effects; Serotonin - analogs & derivatives; Serotonin - pharmacology; Serotonin Receptor Agonists - pharmacology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Synaptic Transmission - radiation effects; Tyrosine 3-Monooxygenase - metabolism; Ventral Tegmental Area - cytology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.4331-05.2006

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 kappa-opioid agonist (5alpha,7alpha,8alpha)-(+)-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 mu/delta opioid agonist [Met5] enkephalin (ME; 3 microM). 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.