The effect of zeta inhibitory peptide (ZIP) on cocaine induced neuroadaptations in the nucleus accumbens

• Applicant: Dr. Andre Deutschmann
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Anatomy and Physiology
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 367294095

• Final Report Year: 2019

Final Report Abstract

The current study establishes that ZIP can rescue two forms of LTD that are disrupted by cocaine self-administration. We suggest that the ability of ZIP to restore the capacity to weaken synaptic input may underlie its behavioral effects. The results of this project have that ZIP can rescue the disruption of long-lasting plasticity induced by cocaine which can lead to the long-lasting disruption in reinstatement in cocaine seeking. Interestingly, an unexpected result of this study was that modification of O-GlcNAcylation in the nucleus accumbens can induce long-term depression independent from ZIP’s effect. For future studies it is very interesting to examine the mechanism behind this effect and if O-GlcNAcylation has an impact on addictive behavior as well. The studies outlined here have provided us with some insight into the mechanism of ZIP-induced blunting of cocaine relapse behavior. However, as ZIP can have widespread influences on learning and memory when administered systemically, it cannot be used in humans at this time. The goal of this project and future directions is to learn more about the mechanisms and work towards developing a more specific drug that would not have the side effects of ZIP.

Publications

• Reversing cocaine-induced plasticity with zeta inhibitory peptide. Journal of Neuroscience 13 August 2019, 1367-19
  Deutschmann, Andre U.; Lenz, Jeffrey D.; McGrath, Anna G. & Briand, Lisa A.