Author

Aya Matsui

Date

October 2012

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Dopamine neurons in ventral tegmental area (VTA) and substantia nigra play a key role in motivation and reward learning. The activation of the mesolimbic dopamine system is the key neuronal circuit that develops adaptive synaptic modification leading to drug addiction. Opioids increase dopamine neuron activity in the mesolimbic system by inhibiting presynaptic GABA terminals. This opioid disinhibition of dopamine neurons is a key first step to result in long-term synaptic adaptations. Therefore, characterizing how opioids increase dopamine neuron activity is crucial for elucidating mechanisms of opioid addiction. There are several GABA inputs in VTA that can be inhibited by opioids. Historically, interneurons in VTA are thought to be a main source of opioid disinhibition of dopamine neurons. Strong GABA inputs also arise from striatum although it is still not clear whether those inputs terminate on dopamine or nondopamine neurons in VTA. μ-opioid receptors are expressed in striatum a

Identifier

doi:10.6083/M41J97S8

Division

Neuroscience Graduate Program

School

School of Medicine

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