Lead author Jennifer Wenzel chose a unique way to reproduce the results of previous work she had done at UCSB, where she earned her Ph.D. in 2013. An earlier study used reversible lesions in the BNST and CeA to block the function in these two areas and then examined their effects in a unique animal model of cocaine self-administration.
For that study, the investigators trained rats to run down a custom-built 6-foot-long runway for a daily dose of cocaine. Each day they responded more quickly than the last, demonstrating an increasing motivation to get cocaine.
"Over several trials, however, rats developed an ambivalence about entering the goal box: they rapidly approached the goal but then turned and retreated back toward the start box," Wenzel explained. "These retreats can happen several times before rats finally enter the goal box and receive an injection of cocaine."
This retreat behavior became more and more prevalent as testing continued and reflects the animals' learning that negative effects (the crash) follow the positive effects (euphoria) of cocaine. Blocking the function of the BNST or the CeA resulted in a dramatic decrease in retreat behavior because the negative effects of the drug were blocked.
In the newly published paper, the researchers used drugs that selectively block the action of the neurotransmitter, noradrenaline, in the BNST and CeA rather than the entire function. The results were similar to those in the earlier study. "If you put norepinephrine antagonists directly into the BNST or the CeA, you can prevent or dramatically attenuate the negative effects of cocaine, leaving the positive effects intact," Ettenberg explained. "So the anima
|Contact: Julie Cohen|
University of California - Santa Barbara