Beta-arrestin 1 regulation of reward-motivated behaviors and glutamatergic function
| Autor: | Wendy Walwyn, Ian A. Mendez, Joshua K. Hakimian, Nitish Mittal, Sean B. Ostlund, Timothy J Schallert, Ralph Albert, Ani Minasyan, Gabriel Gonzalez-Fernandez, Nina Desai, Nicole Romaneschi |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
lcsh:Medicine Social Sciences Self Administration Biochemistry Nucleus Accumbens chemistry.chemical_compound Mice Contractile Proteins Mathematical and Statistical Techniques Learning and Memory 0302 clinical medicine Sociology Cocaine Behavioral Conditioning Medicine and Health Sciences Psychology Phosphorylation lcsh:Science beta-Arrestins Mammals Neurons Mice Knockout Multidisciplinary Animal Behavior Behavior Animal Eukaryota Chemistry Behavioral Pharmacology Physical Sciences Vertebrates NMDA receptor Magazines Statistics (Mathematics) Research Article Operant Conditioning General Science & Technology AMPA receptor Nucleus accumbens Biology LIMK1 Research and Analysis Methods Medium spiny neuron Rodents Receptors N-Methyl-D-Aspartate 03 medical and health sciences Glutamatergic Alkaloids Reward Recreational Drug Use MD Multidisciplinary Ifenprodil Animals Learning Mass Media Statistical Methods Pharmacology Behavior Analysis of Variance Beta-Arrestins lcsh:R Chemical Compounds Organisms Cognitive Psychology Biology and Life Sciences Proteins Communications Actins Corpus Striatum Cytoskeletal Proteins 030104 developmental biology chemistry nervous system Amniotes Cognitive Science lcsh:Q Central Nervous System Stimulants Zoology Neuroscience Mathematics 030217 neurology & neurosurgery |
| Zdroj: | Mittal, Nitish; Minasyan, Ani; Romaneschi, Nicole; Hakimian, Joshua K; Gonzalez-Fernandez, Gabriel; Albert, Ralph; et al.(2017). Beta-arrestin 1 regulation of reward-motivated behaviors and glutamatergic function.. PloS one, 12(10), e0185796. doi: 10.1371/journal.pone.0185796. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/26x372n0 PLoS ONE PLoS ONE, Vol 12, Iss 10, p e0185796 (2017) |
| Popis: | The two highly homologous non-visual arrestins, beta-arrestin 1 and 2, are ubiquitously expressed in the central nervous system, yet knowledge of their disparate roles is limited. While beta-arrestin 2 (βarr2) has been implicated in several aspects of reward-related learning and behavior, very little is known about the behavioral function of beta-arrestin 1 (βarr1). Using mice lacking βarr1, we focused on the role of this scaffolding and signal transduction protein in reward-motivated behaviors and in striatal glutamatergic function. We found that βarr1 KO mice were both slower in acquiring cocaine self-administration and in extinguishing this behavior. They also showed deficits in learning tasks supported by a natural food reward, suggesting a general alteration in reward processing. We then examined glutamatergic synaptic strength in WT and KO medium spiny neurons (MSNs) of the Nucleus Accumbens (NAc) shell in naïve animals, and from those that underwent cocaine self-administration. An increase in the AMPA/NMDA (A/N) ratio and a relative lack of GluN2B-enriched NMDARs was found in naïve KO vs WT MSNs. Applying Lim Domain Kinase (LIMK1), the kinase that phosphorylates and inactivates cofilin, to these cells, showed that both βarr1 and LIMK regulate the A/N ratio and GluN2B-NMDARs. Cocaine self-administration increased the A/N ratio and GluN2B-NMDARs in WT MSNs and, although the A/N ratio also increased in KO MSNs, this was accompanied by fewer GluN2B-NMDARs and an appearance of calcium-permeable AMPARs. Finally, to examine the consequences of reduced basal GluN2B-NMDARs in reward-processing seen in KO mice, we chronically infused ifenprodil, a GluN2B antagonist, into the NAc shell of WT mice. This intervention substantially reduced food-motivated behavior. Together these findings identify a previously unknown role of βarr1 in regulating specific reward-motivated behaviors and glutamatergic function. |
| Databáze: | OpenAIRE |
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