Acetylcholine enhancement in the nucleus accumbens prevents addictive behaviors of cocaine and morphine
Hikida T, Kitabatake Y, Pastan I, Nakanishi S.
Department of Biological Sciences,
Kyoto University Faculty of Medicine,
Kyoto 606-8501, Japan.
Proc Natl Acad Sci U S A 2003 May 13;100(10):6169-73


Drug addiction poses serious social, medical, and economic problems, but effective treatments for drug addiction are still limited. Cocaine and morphine elevate dopamine levels in the nucleus accumbens (NAc), and the overwhelming actions of dopamine are implicated in reinforcement and addiction of abusive drugs. In our previous studies, we reported the regulatory role of acetylcholine (ACh) in the NAc function by selectively ablating the NAc cholinergic neurons with use of immunotoxin-mediated cell targeting. These studies indicated that ACh and dopamine acted convergently but oppositely on the NAc circuit and that cholinergic cell ablation enhanced long-lasting behavioral changes of cocaine addiction. In this investigation, we showed that immunotoxin-mediated ablation of the NAc cholinergic neurons enhanced not only the sensitivity to morphine in conditioned place preference but also negative reinforcement of morphine withdrawal in conditioned place aversion. Remarkably, acetylcholinesterase (AChE) inhibitors that act on the brain AChE suppressed both cocaine- and morphine-induced conditioned place preference and blocked the induction and persistence of cocaine-evoked hyperlocomotion. Importantly, this inhibition was abolished by ablation of the NAc cholinergic neurons. These results demonstrate that centrally active AChE inhibitors prevent long-lasting behavioral abnormalities associated with cocaine and morphine addictions by potentiating the actions of ACh released from the NAc cholinergic neurons. Centrally active AChE inhibitors could thus be approached as novel and potential therapeutic agents for drug addiction.

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Dopaminergic agents
The coke-craving brain
Monoamines, cocaine and rats
Freebasing flies go hyperkinetic
Cocaine and acetylcholine turnover
The bacterial junkie: Rhodococcus sp. strain MB1

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and further reading
Future Opioids
BLTC Research
Utopian Surgery?
The Good Drug Guide
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World