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S059-2

Nicotine Receptor as A Potential Target for Treatment of Pathological
Decision-Making in Addiction

Hiroyuki Mizoguchi1, Kiyofumi Yamada2

1Research Institute of Environmental Medicine, Nagoya University, Japan 2Department of
Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan

Background/Objective: Impaired decision-making is a symptomatic feature of a number of
psychiatric disorders such as drug dependence. However, it is unknown whether impairments of
decision-making and the underlying neural substrates are preexisting condition and contribute to the
initiation of drug use or are a consequence of the repeated use of drugs of abuse.

Method: Nicotine is hypothesized to have therapeutic effects on attentional and cognitive
abnormalities in psychosis. We have also demonstrated that nicotine significantly ameliorated
methamphetamine (METH)-induced disruption to prepulse inhibition and spatial working memory in
rats that had previously received repeated METH treatment.

Result: Here, we examine the effects of nicotine on impaired decision-making in METH-treated rats.
We analyzed the performance of rats in a gambling test for rodents. Rats were given METH
subcutaneously at a dose of 4 mg/kg once a day for 30 days. METH-treated rats chose a
high-risk/high-reward option more frequently, and assigned higher value to high returns, than control
rats, suggesting that changes in choice strategy in decision-making. Interestingly, nicotine
treatment ameliorated the abnormal choice behavior of METH-treated rats in the gambling test.

Conclusion: Our findings suggest that METH modulates perceived values of both reward and risk,
leading to impairments of decision-making. Nicotine may have some therapeutic effects against
impairment of decision-making in METH addicts.