Differential Effects of Lesions in the Subareas of Medial Prefrontal Cortex on the Development of Behavioral Sensitization to Amphetamine: Role of Environmental Context

Abstract

Based on the notion of the heterogeneity of the medial prefrontal cortex (mPFC), the effects of lesions of the dorsal and ventral subareas of mPFC were examined on the development of behavioral sensitization induced by d-amphetamine (AMP). The first part of this study determined behavioral sensitization to AMP by the use of the rat with intermittent repeated AMP administrations in three types of environmental context including an infrared locomotor activity test-box, the home cage, and a novel third place. In experimental groups, each subject was initially injected with AMP of 0.5 mg/kg as the pretest treatment and then received seven injections of AMP (1 mg/kg) every other day in the context where it was assigned. Following two days of withdrawal, the subject was challenged by AMP of 0.5 mg/kg as the post-test treatment. Behavioral sensitization to AMP on the locomotor activity was determined by the difference between pre- and post-test. The results showed that the most profound locomotor sensitization to AMP appeared in the test box group. A less but significant degree of locomotor sensitization to AMP was observed for the home cage group. A trend of locomotor sensitization to AMP observed in the novel third place group was not statistically confirmed. In the second part of experiment, we then investigated the effects of lesions in the dorsal and ventral mPFC subareas on the development of locomotor sensitization to AMP in the test box and home cage. Results showed that locomotor sensitization was significantly appeared in every sham-operated control group tested in either test box or home cage. Lesions of ventral mPFC significantly inhibited the development of locomotor sensitization to AMP in test box, but not in home cage. Lesions of dorsal mPFC failed to affect AMP locomotor sensitization developed in either test box or home cage. These data indicate that the heterogeneous functions of mPFC subareas involved in the development of behavioral sensitization to AMP are dependent on different contexts applied for repeated intermittent drug administration.