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Pleiotrophin differentially regulates the rewarding and sedative effects of ethanol
Author(s) -
VicenteRodríguez Marta,
PérezGarcía Carmen,
FerrerAlcón Marcel,
Uribarri María,
SánchezAlonso María G.,
Ramos María P.,
Herradón Gonzalo
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12841
Subject(s) - pleiotrophin , conditioned place preference , ethanol , chemistry , long term potentiation , apomorphine , knockout mouse , sedative , hippocampus , pharmacology , neuroscience , agonist , receptor , biochemistry , psychology , biology , growth factor
Pleiotrophin (PTN) is a cytokine with important roles in dopaminergic neurons. We found that an acute ethanol (2.0 g/kg, i.p.) administration causes a significant up‐regulation of PTN mRNA and protein levels in the mouse prefrontal cortex, suggesting that endogenous PTN could modulate behavioural responses to ethanol. To test this hypothesis, we studied the behavioural effects of ethanol in PTN knockout (PTN −/− ) mice and in mice with cortex‐ and hippocampus‐specific transgenic PTN over‐expression (PTN‐Tg). Ethanol (1.0 and 2.0 g/kg) induced an enhanced conditioned place preference in PTN −/− compared to wild type mice, suggesting that PTN prevents ethanol rewarding effects. Accordingly, the conditioning effects of ethanol were completely abolished in PTN‐Tg mice. The ataxic effects induced by ethanol (2.0 g/kg) were not affected by the genotype. However, the sedative effects of ethanol (3.6 g/kg) tested in a loss of righting reflex paradigm were significantly reduced in PTN‐Tg mice, suggesting that up‐regulation of PTN levels prevents the sedative effects of ethanol. These results indicate that PTN may be a novel genetic factor of importance in alcohol use disorders, and that potentiation of the PTN signalling pathway may be a promising therapeutic strategy in the treatment of these disorders.Ethanol up‐regulates pleiotrophin (PTN), a cytokine important for dopaminergic neurons, in the prefrontal cortex. Ethanol rewarding effects are abolished in mice over‐expressing PTN and enhanced in PTN −/− mice. The results suggest that up‐regulation of PTN in the prefrontal cortex after ethanol administration serves to modulate ethanol effects in the reward system and other ethanol‐induced pharmacological effects including sedation.