Amphetamine sensitization is accompanied by an increase in prelimbic cortex activity

• Amphetamine sensitized rats show higher basal firing rate in PL neurons.
• Acute amphetamine induces a decrease in firing rate of PL neurons in control rats.
• Acute amphetamine induces an increase in firing rate of PL neurons in sensitized rats.
• Amphetamine sensitization renders PL neurons hyperexcitable.

Drug addiction is associated with dysfunction in the medial prefrontal cortex (mPFC). However, the modifications of neuronal activity in mPFC underlying the reinforcing properties of addictive drugs are still unclear. Here we carried out single-unit recording experiments to study the neuronal activity in the prelimbic (PL) cortex of anesthetized rats, after expression of locomotor sensitization to amphetamine. In control rats, an acute injection of amphetamine induced mainly an inhibitory effect on firing rate (FR) and this response was negatively correlated with the basal FR. Sensitized rats showed a higher proportion of excited neurons and the response to amphetamine was independent of basal FR. Moreover, in control rats, acute amphetamine decreased burst rate, whereas in sensitized rats acute amphetamine increased burst rate. These findings indicate that amphetamine sensitization renders mPFC neurons hyperexcitable. Taken together, these data support the hypothesis that early withdrawal is associated with an increase in the activity of the mPFC, which could strengthen the PL–Nucleus Accumbens connection, thus facilitating amphetamine-induced locomotor sensitization.