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In the new study, Kauer’s team of scientists at Brown and the University of Wyoming made observations both in behaving rats and in rat brain tissue to focus on how stress appears to trigger these receptors to cause relapse, how that relapse remains sustained and how that effect can be disrupted.The study focused on the ventral tegmental area (VTA), where the brain reinforces behaviors related to fulfilling basic needs.
At the heart of the study are kappa opioid receptors (κORs) on the surface of key brain cells.
The κORs are already seen as targets for anti-addiction medication development, but to make effective therapies, researchers must pinpoint specific interactions.
The paper’s lead author is Abigail Polter, formerly of Kauer’s lab and now at George Washington University.
Additional authors are Kelsey Barcomb and Rudy Chen at Brown; Nicholas M Graziane, formerly at Brown and now at the University of Pittsburgh; and Paige Dingess and Travis Brown of the University of Wyoming.
They also showed that merely blocking dynorphin from binding to κORs did not restore GABAergic neuron activity and would therefore not be a productive drug development strategy.
In another experiment, they showed that while relapse can be prevented by blocking dynorphin release before stress occurs, blocking dynorphin release after stress occurs does no good. Given their evidence, what Kauer’s team theorizes is that stress, via dynorphin, flips a switch on κORs that turns off normal GABA signaling at the relevant synapses for days.
The findings, published in the journal suggest a new way to develop medicines to combat relapse, even a day or so after stress has occurred.
“That’s so critical because you don’t want to be taking medication all the time in anticipation of stress,” said senior author Julie Kauer, a professor of molecular pharmacology, physiology and biotechnology at Brown University.
There is great risk when using any form of cocaine, but crack cocaine is the riskiest form of the substance.
Smoking a substance allows it to reach the brain more quickly than other routes of administration, and compulsive cocaine use will develop even more rapidly if the substance is smoked rather than snorted.