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Inhibition of Receptor Protein Tyrosine Phosphatase β/ζ Reduces Alcohol Intake in Rats
Author(s) -
CallejaConde Javier,
FernándezCalle Rosalía,
Zapico José M.,
Ramos Ana,
PascualTeresa Beatriz,
Bühler KoraMareen,
EcheverryAlzate Victor,
Giné Elena,
Rodríguez de Fonseca Fernando,
LópezMoreno Jose Antonio,
Herradón Gonzalo
Publication year - 2020
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14321
Subject(s) - pleiotrophin , midkine , alcohol , self administration , receptor , saccharin , alcohol intake , endocrinology , medicine , signal transduction , chemistry , pharmacology , biochemistry , growth factor
Background Pleiotrophin (PTN) and midkine (MK) are cytokines that are up‐regulated in the prefrontal cortex (PFC) after alcohol administration and have been shown to reduce alcohol intake and reward. Both cytokines are endogenous inhibitors of receptor protein tyrosine phosphatase (RPTP) β/ζ (a.k.a. PTPRZ1). Recently, a new compound named MY10 was designed with the aim of mimicking the activity of PTN and MK. MY10 has already shown promising results regulating alcohol‐related behaviors in mice. Methods We have now tested the effects of MY10 on alcohol operant self‐administration and Drinking In the Dark‐Multiple Scheduled Access (DID‐MSA) paradigms in rats. Gene expression of relevant genes in the PTN/MK signaling pathway in the PFC was analyzed by real‐time PCR. Results MY10, at the highest dose tested (100 mg/kg), reduced alcohol consumption in the alcohol operant self‐administration paradigm ( p = 0.040). In the DID‐MSA paradigm, rats drank significantly less alcohol ( p = 0.019) and showed a significant decrease in alcohol preference ( p = 0.002). We observed that the longer the exposure to alcohol, the greater the suppressing effects of MY10 on alcohol consumption. It was demonstrated that the effects of MY10 were specific to alcohol since saccharin intake was not affected by MY10 ( p = 0.804). MY10 prevented the alcohol‐induced down‐regulation of Ptprz1 ( p = 0.004) and anaplastic lymphoma kinase ( Alk ; p = 0.013) expression. Conclusions Our results support and provide further evidence regarding the efficacy of MY10 on alcohol‐related behaviors and suggest the consideration of the blockade of RPTPβ/ζ as a target for reducing excessive alcohol consumption.