Lesions of the medial prefrontal cortex prevent the induction but not expression of morphine-induced behavioral sensitization in mice.

Repetitive exposure to morphine induces behavioral sensitization, which is supposed to involve in the process of addiction to drugs. As the underlying neuropharmacological mechanisms and anatomical substrates are considerably different between different drugs and different phases of behavioral sensitization, this study was designed to investigate the roles of the medial prefrontal cortex in the induction and expression of morphine-induced behavioral sensitization in mice. In experiments 1 and 2, mice were dosed with morphine (10 mg/kg, i.p.) once daily for 7 continuous days after induction of sham or kainic acid lesions of the medial prefrontal cortex. Locomotor activity was measured on days 1 and 7 to test acute morphine-induced hyperactivity and the induction of behavioral sensitization. In experiment 3, mice were subjected to surgery after behavioral sensitization was achieved. The mice were challenged with morphine 7 days later to evaluate the expression of behavioral sensitization. The results showed that lesions of the medial prefrontal cortex (mPFC) blocked acute morphine-induced hyperactivity and the induction of behavioral sensitization, but the lesions had no effect on the expression of behavioral sensitization. These results provide the first direct evidence that the mPFC may be involved in the induction, but not the expression, of morphine-induced behavioral sensitization.