Mechanisms and functional roles of drug-induced neuroplasticity in the brainstem cholinergic neurons

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Hokkaido University
• Principal Investigator: KANEDA Katsuyuki 北海道大学, 薬学研究科(研究院), 准教授 (30421366)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 薬物依存 / 神経可塑性 / 背外側被蓋核 / 腹側被蓋野 / 報酬系

Outline of Final Research Achievements

The involvement and plasticity of the mesocorticolimbic dopamine (DA) system in cocaine-induced addiction have been studied extensively. However, it remains largely unexplored that the role of the brainstem cholinergic system in cocaine addiction. The laterodorsal tegmental nucleus (LDT) contains cholinergic neurons that innervate the ventral tegmental area (VTA) and is crucial for regulating the activity of VTA DA neurons, implying that LDT may also be associated with cocaine addiction. In this study, we found that cholinergic transmission from the LDT to the VTA is involved in acquisition and expression of cocaine-induced conditioned place preference and that, after repeated cocaine exposures, these neurons exhibit synaptic plasticity, which is dependent on NMDA receptor activation, nitric oxide production, and the activity of medial prefrontal cortex. The findings strongly suggest that LDT cholinergic neurons may be critically involved in developing cocaine-induced addiction.

Free Research Field

神経薬理学