Stimulating brain cells prevents compulsive cocaine seeking

2013

Challenge

Loss of control is one of the most intractable aspects of addiction, as substance abusers continue to pursue drugs despite incurring significant negative consequences. Human studies have suggested that deficient brain function in the prefrontal cortex leading to loss of inhibition could be promoting compulsive drug use. However, it remained unknown whether chronic drug use compromises cortical activity and if such a deficit leads to compulsive cocaine seeking.

Advance

IRP researchers led by Antonello Bonci, M.D., explored the relationship between drug use and cortical activity with a rat model of compulsive drug seeking, in which cocaine seeking persists despite the delivery of foot shocks. They showed that prolonged self-administration of cocaine decreases the excitability of neurons deep within the prelimbic cortex, an effect even more pronounced in compulsive drug-seeking animals. When the researchers stimulated those neurons with optogenetics, they observed a decrease in compulsive cocaine seeking, whereas inhibition of the neurons significantly increased compulsive cocaine seeking.

Impact

The team’s results provide a basis for transcranial magnetic stimulation (TMS) clinical studies in humans, which would aim to stimulate the prelimbic cortex as a potential novel therapy for treating compulsive drug use.

Publications

Chen BT, Yau HJ, Hatch C, Kusumoto-Yoshida I, Cho SL, Hopf FW, Bonci A. (2013). Rescuing cocaine induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking. Nature. 496(7445), 359-62.