Repeated cocaine exposure increases fast-spiking interneuron excitability in the rat medial prefrontal cortex

The medial prefrontal cortex plays a key role in cocaine addiction. However, how chronic cocaine exposure affects cortical networks remains unclear. Most studies have focused on layer 5 pyramidal neurons (the circuit output), while the response of local GABAergic interneurons to cocaine remains poorly understood. Here, we recorded from fast-spiking interneurons (FS-IN) after repeated cocaine exposure and found altered membrane excitability. After cocaine withdrawal, FS-IN showed an increase in the number of spikes evoked by positive current injection, increased input resistance, and decreased hyperpolarization-activated current. We also observed a reduction in miniature excitatory postsynaptic currents, whereas miniature inhibitory postsynaptic current activity was unaffected. We show that, in animals with cocaine history, dopamine receptor D-2 activation is less effective in increasing FS-IN intrinsic excitability. Interestingly, these alterations are only observed 1 wk or more after the last cocaine exposure. This suggests that the dampening of D-2 -receptor-mediated response may be a compensatory mechanism to rein down the excitability of FS-IN.