Human studies suggest that deficits in prefrontal cortical function and the resulting loss of inhibitory control could be crucial in promoting compulsive drug use. However, it is unclear whether chronic drug use compromises cortical activity and whether this deficit promotes compulsive cocaine seeking.

In this report, Chen and colleagues study a rat model of compulsive drug seeking in which cocaine seeking persists in a subgroup of rats despite noxious foot shocks. They show that prolonged cocaine self-administration decreases ex vivo intrinsic excitability of deep-layer pyramidal neurons in the prelimbic cortex, and this was significantly more pronounced in compulsive drug-seeking animals.

In vivo optogenetic prelimbic cortex stimulation (which compensates for hypoactive prelimbic cortical neurons) significantly prevented compulsive cocaine seeking, whereas optogenetic prelimbic cortex inhibition was associated with increased compulsive cocaine seeking. The authors suggest that targeted stimulation of the prefrontal cortex could serve as a promising therapy for treating compulsive drug use.

Chen BT, Yau H-J, Hatch C, Kusumoto-Yoshida I, Cho SL, Woodward Hopf F, Bonci A: Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking. Nature [Epub ahead of print April 3, 2013; doi:10.1038/nature12024].

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