Effect of drugs of abuse on reward-based decision-making in rodents

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In the present study, we developed a gambling testfor rodents using a radial-arm maze to address the issue of decision-making in patients with drug dependence. Rats were trained in the cost/benefit decision-making task, in which they chose one of four arms [one low risk/low return (LL) arm, one high risk/high return (HH) arm and two empty arms]. The test consisted of consecutive 16 trials a day. Following extensive testing, naive rats showed the choice behavior, which is dependent on reward probability and reward value of the arms. Following chronic treatment with methamphetamine, the animals chose HH arms more frequently than did saline-treated control rats. After the gambling test, c-Fos expression was markedly increased in the insular cortex, striatum, and nucleus accumbens of methamphetamine-dependent rats compared to saline-treated control rats. Our findings suggest that chronic methamphetamine treatment may lead to alternations of reward-based decision-making. Aberrant activation of the cortico-striatal pathway from insular cortex to striatum may be associated with the impairment of reward-based decision-making in methamphetamine-dependent rats.