RT Journal Article
T1 Inhibition of receptor protein tyrosine phosphatase β/ζ reduces alcohol intake in rats
A1 Calleja Conde, Javier
A1 Fernández Calle, Rosalía
A1 Zapico, José M.
A1 Ramos, Ana
A1 Pascual Teresa, Beatriz de
A1 Buhler, Kora Mareen Katharina
A1 Echeverry Alzate, Victor
A1 Giné Domínguez, Elena
A1 Rodríguez De Fonseca, Fernando Antonio
A1 López Moreno, José Antonio
A1 Herradón, Gonzalo
AB 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.
PB Wiley
SN 0145-6008
SN 1530-0277
YR 2020
FD 2020-03-27
LK https://hdl.handle.net/20.500.14352/130583
UL https://hdl.handle.net/20.500.14352/130583
LA eng
NO Calleja‐Conde, J., Fernández‐Calle, R., Zapico, J. M., Ramos, A., De Pascual‐Teresa, B., Bühler, K., Echeverry‐Alzate, V., Giné, E., Rodríguez De Fonseca, F., López‐Moreno, J. A., & Herradón, G. (2020). Inhibition of receptor protein tyrosine phosphatase β/ζ reduces alcohol intake in rats. Alcoholism: Clinical and Experimental Research, 44(5), 1037-1045. https://doi.org/10.1111/acer.14321
NO This is the peer reviewed version of the following article: Calleja‐Conde, J., Fernández‐Calle, R., Zapico, J. M., Ramos, A., De Pascual‐Teresa, B., Bühler, K., Echeverry‐Alzate, V., Giné, E., Rodríguez De Fonseca, F., López‐Moreno, J. A., & Herradón, G. (2020). Inhibition of receptor protein tyrosine phosphatase β/ζ reduces alcohol intake in rats. Alcoholism: Clinical and Experimental Research, 44(5), 1037-1045, which has been published in final form at  https://doi.org/10.1111/acer.14321. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
NO Ministerio de Sanidad (España)
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 29 mar 2026