Discovery of new neural pathway may lead to preventing relapses in addicts.
Researchers at the University at Buffalo have discovered a previously unknown neural pathway that can regulate changes made in the brain due to cocaine use, providing new insight into the molecular basis of cocaine addiction.
“Addiction is a life-long affliction manifested by episodes of relapse, despite prolonged abstinence,” says Amy Gancarz, PhD, lead author of the study, which was published on June 1 in an Advance Online Publication in Nature Neuroscience. “There is a need to more fully understand the long-term molecular changes in the brain involved in drug craving and relapse.”
Gancarz, a former postdoctoral associate with the UB Research Institute on Addictions (RIA), worked on the study under the direction of senior author David Dietz, PhD, assistant professor in the Department of Pharmacology and Toxicology in UB’s School of Medicine and Biomedical Sciences. Dietz is also a faculty member in UB’s Neuroscience Program and an affiliated scientist with RIA.
The study found that by manipulating the activity of Activin receptors — receptors found in the brain — the researchers were able to increase or decrease cocaine-taking and relapse behavior in animal models. The study focused, specifically, on Activin receptors in regions of the brain that are involved in pleasure and reward.
“There are changes in the brain caused by drug use that occur and persist, but are only unmasked after withdrawal from a drug — in this case, cocaine,” Dietz says. “Cocaine use alters the connections between certain neurons through changes in the shape of the cells.”
The researchers discovered that the Activin pathway controls the ability of cocaine to induce this change in the neurons and determined that the Activin receptor may control this response to cocaine by regulating the expression of a number of genes.
“Understanding this critical pathway will help us pursue new directions in potential pharmacological and gene therapies to prevent drug relapses,” Dietz says. “If we can control this pathway, we may be able to help prevent relapses in people who have been abstinent from cocaine.”
Study co-authors include Zi-Jun Wang, PhD, Gabrielle L. Schroeder, PhD, Kevin M. Braunscheidel, PhD, Lauren E. Mueller, PhD, Monica S. Humby, PhD, Aaron Caccamise, PhD, Jennifer A. Martin, PhD, and Karen C. Dietz, PhD, of the UB Department of Pharmacology and Toxicology; Diane Damez-Werno, PhD, of the Icahn School of Medicine at Mount Sinai, New York; and Rachael L. Neve, PhD, of the Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology.
Source: Cathy Wilde – University at Buffalo
Image Credit: Image is credited to Mikael Häggström
Original Research: Abstract for “Activin receptor signaling regulates cocaine-primed behavioral and morphological plasticity” by Amy M Gancarz, Zi-Jun Wang, Gabrielle L Schroeder, Diane Damez-Werno, Kevin M Braunscheidel, Lauren E Mueller, Monica S Humby, Aaron Caccamise, Jennifer A Martin, Karen C Dietz, Rachael L Neve and David M Dietz in Nature Neuroscience. Published online June 1 2015 doi:10.1038/nn.4036
Abstract
Activin receptor signaling regulates cocaine-primed behavioral and morphological plasticity
Activin receptor signaling, including the transcription factor Smad3, was upregulated in the rat nucleus accumbens (NAc) shell following withdrawal from cocaine. Direct genetic and pharmacological manipulations of this pathway bidirectionally altered cocaine seeking while governing morphological plasticity in NAc neurons. Thus, Activin/Smad3 signaling is induced following withdrawal from cocaine, and such regulation may be a key molecular mechanism underlying behavioral and cellular plasticity in the brain following cocaine self-administration.
“Activin receptor signaling regulates cocaine-primed behavioral and morphological plasticity” by Amy M Gancarz, Zi-Jun Wang, Gabrielle L Schroeder, Diane Damez-Werno, Kevin M Braunscheidel, Lauren E Mueller, Monica S Humby, Aaron Caccamise, Jennifer A Martin, Karen C Dietz, Rachael L Neve and David M Dietz in Nature Neuroscience. Published online June 1 2015 doi:10.1038/nn.4036
