title: Pleiotrophin differentially regulates the rewarding and sedative effects of ethanol.
abstract: 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.
authors: Pharmacology lab, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
authors: Marta
authors: M
authors: Vicente-Rodríguez
authors: Carmen
authors: C
authors: Pérez-García
authors: Marcel
authors: M
authors: Ferrer-Alcón
authors: María
authors: M
authors: Uribarri
authors: María G
authors: MG
authors: Sánchez-Alonso
authors: María P
authors: MP
authors: Ramos
authors: Gonzalo
authors: G
authors: Herradón
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000172:deficiency* / Q000235:genetics; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006993:Hypnotics and Sedatives / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000276:immunology; D012201:Reward; D045442:Rotarod Performance Test; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D006993:Hypnotics and Sedatives; D012333:RNA, Messenger; C066845:pleiotrophin; D000431:Ethanol
keywords: ALK; addiction; alcohol; conditioned place preference; dependence; midkine