U of M researchers find repeated cocaine use weakens inhibitory signaling in the brain

Wednesday, October 2, 2013

Repeated cocaine treatment alters inhibitory neurotransmission in the brain in long-lasting manner, which may have an impact on behavior control, shows new research out of the University of Minnesota.

The study, published today in the journal Neuron, highlights a newly discovered way in which repeated cocaine exposure alters neurotransmission in the brain. While many studies have shown cocaine alters excitatory neurotransmission in the brain’s “reward circuitry,” this new paper shows that repeated exposure suppresses inhibitory neurotransmission in the prefrontal cortex, a region of the brain that plays a key role in decision-making and behavioral control.

“We found the adaptation in the prefrontal cortex was both selective and very durable, lasting more than a month after the final injection,” said Kevin Wickman, Ph.D., professor of pharmacology in the University of Minnesota Medical School and the principle investigator on this project. “These findings may help explain some of the behaviors associated with long-term drug exposure, including cravings and propensity for relapse.”

Researchers took these findings and sought to mimic an addicted state in mice that had not been exposed to drugs. By selectively suppressing the function of a potassium-selective ion channel called the Girk channel in a specific region of the prefrontal cortex, they were able to induce a behavioral state similar to the mice given repeated cocaine injections.

The findings indicate the suppressing Girk channel activity in the prefrontal cortex may represent a key step in the development of addiction-related behavior.

“Our findings indicate that Girk channels may be an effective target for addiction therapies, such as drugs that selectively open or close Girk channels within select neuron populations of the brain that may promote active decision-making and permit the addict to choose not to take the drug,” said Matthew Hearing, Ph.D., a postdoctoral associate in the Department of Neuroscience and first author on this paper. “Further research is needed to determine how cocaine-induced adaptations in prefrontal cortex Girk signaling alter other areas of the ‘reward circuit’, and how this relates to compulsive drug taking.”

Funding for this project was provided by National Institutes of Health grants to the authors, including MH061933, DA011806, DA029343 and DA007097. The Spanish Ministry of Science and Innovation (BFU2012-38348) and CONSOLIDER-Ingenio (CSD2008-0000) also contributed to this project.