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Our previous findings showed that medial PFC (mPFC) neurons in rats treated repeatedly with amphetamine exhibit a decreased inhibitory response to iontophoretically applied DA, demonstrating altered DA receptor transmission. To determine the role postsynaptic DA D<jats:sub>1<\/jats:sub>receptors play in this effect, we used whole-cell patch-clamp recordings of acutely dissociated pyramidal mPFC neurons and inhibition of transient voltage-sensitive sodium current (<jats:italic>I<\/jats:italic><jats:sub>NaT<\/jats:sub>) as a measure of D<jats:sub>1<\/jats:sub>receptor function. After 3 d of withdrawal, neurons recorded from amphetamine-treated rats (5 mg\/kg for 5 d) demonstrated a significant decrease in whole-cell<jats:italic>I<\/jats:italic><jats:sub>NaT<\/jats:sub>density and in the ability of D<jats:sub>1<\/jats:sub>receptor stimulation to inhibit<jats:italic>I<\/jats:italic><jats:sub>NaT<\/jats:sub>. Application of a protein kinase A (PKA) inhibitor blocked the ability of D<jats:sub>1<\/jats:sub>receptor activation to inhibit<jats:italic>I<\/jats:italic><jats:sub>NaT<\/jats:sub>and increased the current density of both groups to similar values. These results suggest that repeated amphetamine exposure results in subsensitivity of the<jats:italic>I<\/jats:italic><jats:sub>NaT<\/jats:sub>to D<jats:sub>1<\/jats:sub>receptor-mediated inhibition because of a possible increase in basal PKA activity. This adaptation may contribute to perseverative behaviors in animals that self-administer psychostimulants as well as compromised PFC-dependent behaviors in human addicts.<\/jats:p>","DOI":"10.1523\/jneurosci.2375-05.2006","type":"journal-article","created":{"date-parts":[[2006,3,22]],"date-time":"2006-03-22T20:18:20Z","timestamp":1143058700000},"page":"3164-3168","source":"Crossref","is-referenced-by-count":31,"title":["Repeated Amphetamine Administration Decreases D<sub>1<\/sub>Dopamine Receptor-Mediated Inhibition of Voltage-Gated Sodium Currents in the Prefrontal Cortex"],"prefix":"10.1523","volume":"26","author":[{"given":"Jayms D.","family":"Peterson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina E.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis 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