The Neural Mechanism Of Nicotine-induced Abnormality In Decision-making

Drug addiction presents as a chronic relapsing disorder characterized by persistent drug-seeking and drug-taking behaviours.Deficits in the computational processes of reinforcement learning have been suggested to underlie addiction.Previous studies found that impairments in uncertainty modulation in the ACC disrupt reinforcement learning processes in chronic nicotine users and contribute to maladaptive decision-making.The goal in the present study was to explore the neural mechanisms underlying this deficit.In Experiment I,We established the model of nicotine addiction in rats based on the conditioned place preference(CPP).Nicotine-induced CPP can be established in rats.Once established,nicotine-induced CPP was extinguished by repeated testing.Following this extinction phase,the reinstatement of CPP was investigated.It show that model of nicotine addiction was established successfully.In experiment II,nicotine group rats and control group rats accomplished the Rat Gambling Task(RGT),and serotonin and dopamine receptor mRNA expression in the ACC was analyzed by Quantitative RT-PCR.We found that the control group systematically preferred advantageous options over time while the nicotine-addiction group did not preferred in RGT.The result of Quantitative RT-PCR found that serotonin,but not dopamine,receptor mRNA expression significantly decreased in the ACC of the nicotine exposed compared to the control rats.Furthermore,there was a positive correlation between learning rate and serotonin receptor mRNA expression in the ACC.In experiment III,we assessed the effects of modified IGT using water as the reward in human participants.We found that the choice patterns did not differ between the money IGT and our modified water IGT.This suggest that similar cognitive processes and resources may be recruited to solve the tasks in humans and rats.These findings support interventions for pathological decision-making in drug addiction that strongly focus on the serotonin system in ACC.