title: Attenuation of cocaine-induced conditioned locomotion is associated with altered expression of hippocampal glutamate receptors in mice lacking LPA1 receptors.
abstract: BACKGROUND
  Lysophosphatidic acid is a phospholipid mediator that modulates neurodevelopment and neurogenesis in the hippocampus through its actions on LPA1 receptors. Emerging evidences support LPA(1) as a mediator of learning and emotional behaviour. There are no studies addressing its role on behaviours associated to drug abuse.
  
  
  OBJECTIVE
  We examined whether genetic deletion of LPA1 receptor in maLPA(1)-null mice affected either cocaine-induced conditioned locomotion (CL) or behavioural sensitization (BS) induced by repeated cocaine exposure. We also analysed whether cocaine induced changes in the expression of functional markers of both dopamine- and glutamate-related genes in the striatum and the dorsal hippocampus.
  
  
  METHODS
  We monitored cocaine-induced CL and BS in both genotypes of mice. Striatal dopamine and hippocampal glutamate-related genes were measured by real-time quantitative PCR, Western blot, and immunohistochemistry.
  
  
  RESULTS
  maLPA(1)-null mice exhibit an attenuated CL response after cocaine conditioning but a normal BS after repeated cocaine exposure. These behavioural changes were associated to alterations on the expression of metabotropic mGLUR3 glutamate receptors and on the actions of cocaine on the GLUR1 subunit of AMPA glutamate receptors in the hippocampus of maLPA(1) animals. Striatal dopaminergic markers (tyrosine hydroxylase, dopamine D1 receptor, and dopamine transporter DAT), were similar in both genotypes and were equally affected by cocaine exposure.
  
  
  CONCLUSIONS
  The present results indicate that the lack of LPA1 receptor affect cocaine-induced conditioned locomotion but not behavioural sensitization. The findings suggest that LPA1 receptor may be necessary for a normal associative contextual learning associated to cocaine, probably through the modulation of hippocampal glutamatergic circuits.
authors: Fundación IMABIS, Laboratorio de Medicina Regenerativa, Hospital Regional Universitario Carlos Haya, Málaga 29010, Spain. eduardo.blanco@uma.es
authors: Eduardo
authors: E
authors: Blanco
authors: Ainhoa
authors: A
authors: Bilbao
authors: María Jesús
authors: MJ
authors: Luque-Rojas
authors: Ana
authors: A
authors: Palomino
authors: Francisco J
authors: FJ
authors: Bermúdez-Silva
authors: Juan
authors: J
authors: Suárez
authors: Luis J
authors: LJ
authors: Santín
authors: Guillermo
authors: G
authors: Estivill-Torrús
authors: Antonia
authors: A
authors: Gutiérrez
authors: José Angel
authors: JA
authors: Campos-Sandoval
authors: Francisco J
authors: FJ
authors: Alonso-Carrión
authors: Javier
authors: J
authors: Márquez
authors: Fernando Rodríguez
authors: FR
authors: de Fonseca
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000523:psychology; D003213:Conditioning, Psychological / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D017470:Receptors, Glutamate / Q000235:genetics*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*
chemical_list: D017470:Receptors, Glutamate; D049368:Receptors, Lysophosphatidic Acid; D018698:Glutamic Acid; D003042:Cocaine; D004298:Dopamine