Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location
Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location
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DOI：
10.1523/jneurosci.4331-05.2006
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发表时间：
2006-03-08
影响因子：
5.3
通讯作者：
Williams, JT
中科院分区：
文献类型：
--
作者：
Ford, CP;Mark, GP;Williams, JT
介导几乎所有滥用药物的奖励特性的中脑边缘多巴胺系统起源于腹侧被盖区（VTA），并将主要投射发送到丘脑核（NAc）和基底外侧杏仁核（BLA）。为了解决投射到这些不同区域的神经元之间是否存在差异，将逆行微球注射到DBA/2 J小鼠的BLA或NAc中。从标记的VTA多巴胺神经元进行全细胞记录。我们发现，确定的神经元投射到BLA和NAC起源于不同象限的腹侧被盖区，没有一组表现出大幅度的h-电流。投射到NAc的神经元对κ-阿片受体激动剂的反应表现出更大的外向电流（5 α，7 α，8 α）-（+）-N-甲基-N-[7-（吡咯烷基）-1-氧杂螺[4，5]癸-8-基]-苯乙酰胺（U69593; 200 nM），而投射到BLA的神经元对mu/delta阿片激动剂[Met（5）]脑啡肽表现出更大的抑制作用（ME; 3 μ M）。此外，我们还发现U69593对GABA（A）和GABA（B）受体上GABA能传递的突触前抑制作用在两组之间存在差异。当多巴胺IPSC进行了检查，U69593引起了更大的抑制NAc比BLA-profiling神经元。ME对两者都没有影响。最后，多巴胺摄取转运蛋白对细胞外多巴胺的调节在腹侧被盖区是相等的。这些结果表明，阿片类药物差异抑制中脑边缘神经元依赖于他们的目标预测。确定投射中脑边缘腹侧被盖区多巴胺神经元的特性对于理解滥用药物的作用至关重要。
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 (5 alpha,7 alpha,8 alpha)-(+)-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 [Met(5)] enkephalin (ME; 3 mu M). In addition, we found that the presynaptic inhibition of GABAergic transmission at both GABA(A) and GABA(B) 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.