Inhibition of RPTP β/ζ blocks ethanol-induced conditioned place preference in pleiotrophin knockout mice.

Inhibition of RPTPβ/ζ blocks ethanol-induced conditioned place preference in pleiotrophin knockout mice. Behav Brain Res. 2019 May 01;:111933 Authors: Fernández-Calle R, Gramage E, Zapico JM, de Pascual-Teresa B, Ramos A, Herradón G 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 endogenous inhibitors of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ. Interestingly, pharmacological inhibition of RPTPβ/ζ reduces ethanol consumption and blocks ethanol-induced conditioned place preference (CPP) in wild type mice. Since PTN-knockout (Ptn-/-) mice are more sensitive to the conditioning effects of alcohol, we aimed to test the effects of MY10, a small-molecule inhibitor of RPTPβ/ζ, on ethanol-induced CPP in Ptn-/- mice. The data presented here demonstrate for the first time that a regular dose of MY10, known to block ethanol consumption and reward in wild type mice, also blocks the rewarding effects of ethanol in the more vulnerable individuals lacking PTN, the endogenous inhibitor of RPTPβ/ζ. In addition, since MY10 readily penetrates the blood brain barrier (BBB), we tested its effects in a series of behavioural tests in Ptn+/+ and Ptn-/- mice. The data indicate that MY10 does not cause gross behavioural effects in wild type mice. However, MY10 tended to i...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research