Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA.
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Neuron. 2014 Jun 18;82(6):1346-56. doi: 10.1016/j.neuron.2014.04.030. Epub 2014 May 22.
GABA release from interneurons in VTA, projections from the nucleus accumbens (NAc), and rostromedial tegmental nucleus (RMTg) was selectively activated in rat brain slices. The inhibition induced by μ-opioid agonists was pathway dependent. Morphine induced a 46% inhibition of IPSCs evoked from the RMTg, 18% from NAc, and IPSCs evoked from VTA interneurons were almost insensitive (11% inhibition). In vivo morphine treatment resulted in tolerance to the inhibition of RMTg, but not local interneurons or NAc, inputs. One common sign of opioid withdrawal is an increase in adenosine-dependent inhibition. IPSCs evoked from the NAc were potently inhibited by activation of presynaptic adenosine receptors, whereas IPSCs evoked from RMTg were not changed. Blockade of adenosine receptors selectively increased IPSCs evoked from the NAc during morphine withdrawal. Thus, the acute action of opioids, the development of tolerance, and the expression of withdrawal are mediated by separate GABA afferents to dopamine neurons.
GABA 从 VTA 中的中间神经元、核壳（NAc）的投射和延髓背侧正中核（RMTg）释放，在大鼠脑切片中被选择性激活。μ 阿片受体激动剂诱导的抑制作用具有途径依赖性。吗啡诱导来自 RMTg 的 IPSC 抑制 46%，来自 NAc 的 IPSC 抑制 18%，而来自 VTA 中间神经元的 IPSC 几乎不敏感（抑制 11%）。体内给予吗啡治疗导致对 RMTg 的抑制产生耐受性，但对局部中间神经元或 NAc 输入没有影响。阿片类药物戒断的一个常见迹象是腺苷依赖性抑制增加。激活 NAc 中的突触前腺苷受体强烈抑制来自 NAc 的 IPSC，而来自 RMTg 的 IPSC 没有变化。腺苷受体阻断剂选择性地增加吗啡戒断期间来自 NAc 的 IPSC。因此，阿片类药物的急性作用、耐受性的发展和戒断的表达是由多巴胺神经元的不同 GABA 传入介导的。
