Mechanism Underlying Cocaine Addiction– Suppression of Brain Stem Neural Activities Inhibits Drug Cravings

Research Press Release | March 12, 2015

Press Release
Key Points -We discovered a new mechanism underlying the development of drug addiction.

-We discovered that chronic intake of cocaine increased the excitability in the brain at the site called the laterodorsal tagmental nucleus.1

-We further clarified that cocaine cravings can be suppressed by controlling the excitability of the laterodorsal tagmental nucleus.

-From these results, we expect developments leading to treatments for drug addiction.

Overview Drug addiction, caused by illegal drugs, narcotics, and stimulant drugs, is attributed to long-lasting changes in the brain condition (plastic change2). There are many reports about plastic changes which are induced in the key brain region called ‘the brain reward system’.3 However, change in the laterodorsal tagmental nucleus, the site in the brain that controls the reward system activity, has yet to be clarified. At this time, our research group was the first in the world to discover that activity in neurons of the laterodorsal tagmental nucleus increased in rats subjected to chronic administration of cocaine (excitability of membrane was strengthened). Moreover, we discovered that persistent Na+ channels4 were related to this change, and when these channels were blocked, drug cravings in the animals were inhibited. From the achievements of this study, we showed that the laterodorsal tagmental nucleus can be a new target in the treatment of drug addiction which currently has no effective treatment method or medication. This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

1)Laterodorsal tagmental nucleus: A nucleus within the brain stem, comprised of neurons containing acetylcholine, glutamate, and GABA as neurotransmitters. This projects to the dopaminergic neurons in the ventral tegmental area, and controls its activity.

2)Plastic change: Condition of change caused by influence from the outer environment from which recovery does not occur. In this study, the condition where cell excitability remains in the changed (strengthened) state by chronic administration of cocaine.

3)Brain reward system: A neural circuit comprised of the ventral tegmental area and its projection, nucleus accumbens and the medial prefrontal cortex. When this circuit is activated in humans and animals, the “pleasure” emotion is generated. Studies based on the motivation and reward cycle promoted by this emotion are currently underway. On the other hand, excessive activation of this circuit contributes to the development of drug addiction.

4)Persistent Na+ channels: A type of sodium channel which activates neurons, and which the activated condition continues for a long time once opened. Consequently, activation of this channel continuously raises excitability of neuro cells.


Katsuyuki Kaneda, Associate Professor, Department of PharmacologyGraduate School of Pharmaceutical Sciences, Hokkaido University

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 コカイン依存形成のメカニズム -脳幹の神経活動を抑制することで薬物欲求が抑制されることを発見-
Publications Intrinsic membrane plasticity via increased persistent sodium conductance of cholinergic neurons in the rat laterodorsal tegmental nucleus contributes to cocaine-induced addictive behavior, European Journal of Neuroscience (2015.2.24)