2. Academic Validation
  3. Inhibition of Receptor Protein Tyrosine Phosphatase β/ζ Reduces Alcohol Intake in Rats

Inhibition of Receptor Protein Tyrosine Phosphatase β/ζ Reduces Alcohol Intake in Rats

  • Alcohol Clin Exp Res. 2020 May;44(5):1037-1045. doi: 10.1111/acer.14321.
Javier Calleja-Conde 1,  Rosalía Fernández-Calle 2,  José M Zapico 3,  Ana Ramos 3,  Beatriz de Pascual-Teresa 3,  Kora-Mareen Bühler 1,  Victor Echeverry-Alzate 1 4,  Elena Giné 5,  Fernando Rodríguez de Fonseca 4,  Jose Antonio López-Moreno 1,  Gonzalo Herradón 2
Affiliations

Affiliations

  • 1 From the, Department of Psychobiology and Behavioral Sciences Methods, (JC-C, K-MB, VE-A, JAL-M), School of Psychology, Complutense University of Madrid, Madrid, Spain.
  • 2 Departamento de Ciencias Farmacéuticas y de la Salud, (RF-C, GH), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Alcorcón, Spain.
  • 3 Departamento de Química y Bioquímica, (JMZ, AR, BP-T), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Alcorcón, Spain.
  • 4 Laboratorio de Medicina Regenerativa, (VE-A, FRF), Hospital Regional Universitario Carlos Haya, Fundación IMABIS, Málaga, Spain.
  • 5 Department of Cellular Biology, (EG), School of Medicine, Complutense University of Madrid, Madrid, Spain.
PMID: 32154588 DOI: 10.1111/acer.14321
Abstract

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.

Keywords

ALK; Alcohol Use Disorder; Midkine; Pleiotrophin.

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