Amphetamine Sensitization and Prefrontal Cortex Function

University Of Illinois Urbana-Champaign, Champaign IL

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Abstract

DESCRIPTION (provided by applicant): Repeated exposure to psychostimulant drugs such as amphetamine (AMPH) often leads to behavioral sensitization, which refers to enhanced motor responsiveness to subsequent drug administration. Alterations in brain anatomy and function parallel behavior changes and these adaptations have been hypothesized to contribute to the development and maintenance of human drug addiction. A large body of studies, mostly performed in rats, has implicated dopamine- and glutamate-containing brain areas within cortico-limbic and striatal pathways as important anatomical substrates for AMPH-induced behavioral sensitization. In particular, the medial prefrontal cortex (mPFC) appears to play an important role in the induction and expression of behavioral sensitization through its influence on the ventral tegmental area and nucleus accumbens, respectively. Thus, studies of mPFC function in awake, behaving subjects are necessary to verify if drug-induced plasticity in the mPFC is important for behavioral sensitization and if changes in neuronal responses correlate to its induction and/or expression. In the experiments proposed here, we will test the following hypotheses: (1) AMPH has acute effects on mPFC neurons that depend on the neuron's responsiveness during behavior and/or to a particular environmental context, and (2) Behavioral sensitization to repeated, intermittent administration of AMPH is correlated with changes in the firing rate and/or pattern of mPFC neurons and this relationship will differ in non-sensitized animals. We will use chronically implanted, multiwire electrodes to record single-neuron activity in the mPFC of rats that are allowed unrestricted movement in an open-field arena. Recordings will be obtained during baseline conditions, after saline administration, and after rats have undergone either acute or chronic treatment with AMPH. Ultimately, these experiments will help clarify the role of mPFC plasticity in behavioral sensitization and will further our understanding of the neuroadaptations associated with repeated drug intake.