Pharmacological inhibition of Receptor Protein Tyrosine Phosphatase β/ζ (PTPRZ1) modulates behavioral responses to ethanol

Neuropharmacology
Rosalía Fernández-CalleGonzalo Herradón

Abstract

Pleiotrophin (PTN) and Midkine (MK) are neurotrophic factors that are upregulated in the prefrontal cortex after alcohol administration and have been shown to reduce ethanol drinking and reward. PTN and MK are the endogenous inhibitors of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ (a.k.a. PTPRZ1, RPTPβ, PTPζ), suggesting a potential role for this phosphatase in the regulation of alcohol effects. To determine if RPTPβ/ζ regulates ethanol consumption, we treated mice with recently developed small-molecule inhibitors of RPTPβ/ζ (MY10, MY33-3) before testing them for binge-like drinking using the drinking in the dark protocol. Mice treated with RPTPβ/ζ inhibitors, particularly with MY10, drank less ethanol than controls. MY10 treatment blocked ethanol conditioned place preference, showed limited effects on ethanol-induced ataxia, and potentiated the sedative effects of ethanol. We also tested whether RPTPβ/ζ is involved in ethanol signaling pathways. We found that ethanol treatment of neuroblastoma cells increased phosphorylation of anaplastic lymphoma kinase (ALK) and TrkA, known substrates of RPTPβ/ζ. Treatment of neuroblastoma cells with MY10 or MY33-3 also increased levels of phosphorylated ALK and TrkA. However, concomit...Continue Reading

Citations

Oct 17, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Kana Hamada, Amy W Lasek
Mar 11, 2020·Alcoholism, Clinical and Experimental Research·Javier Calleja-CondeGonzalo Herradón
Apr 29, 2020·Alcoholism, Clinical and Experimental Research·Carolina L Haass-Koffler
Jun 3, 2021·International Journal of Molecular Sciences·Julio SevillanoMaría Del Pilar Ramos-Álvarez

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