Evidence of histamine h3 receptor crosstalk with dopamine d1 receptors and group 1 metabotropic glutamate receptors in the brain: possible link with cocaine addiction-like behavior in rodents

• Autores: Hanne Mette Hoffmann
• Directores de la Tesis: Michel Vignes (dir. tes.), Jordi Ortiz de Pablo (dir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2010
• Idioma: español
• Tribunal Calificador de la Tesis: Antonio Armario García (presid.), Francisco Ciruela Alférez (secret.), Yves Audigier (voc.), Michel Vignes (voc.), Jordi Ortiz de Pablo (voc.), Matthew Fizjohn (voc.)
• Materias:
  • Química
    • Bioquímica
      • Biología molecular
  • Psicología
    • Psicología experimental
      • Análisis experimental de la conducta
• Texto completo no disponible (Saber más ...)
• Resumen

  • Alterations of neuronal activity, mediated by G-protein coupled receptors (GPCRs), can modulate neuronal circuits and are thought to be important in the development and expression of diseases as cocaine addiction. GPCR activity is regulated by various mechanisms, including protein-protein interactions in the membrane, permitting these receptors to crosstalk and form homo-and heteromers.

    Cocaine blocks monoamine reuptake leading to increased synaptic presence of various neurotransmitters including dopamine, histamine and glutamate in the brain. First we describe that dopamine D1 receptors (D1R) and histamine H3 receptors (H3R) crosstalk in the rodent brain. Chronic cocaine self-administration altered the crosstalk between D1R and H3R in the striatum, a brain structure involved in habit learning and motor control. The altered signaling was observed in both individual receptor signaling and by D1R-H3R crosstalk signaling.

    Both histamine H¬3R and metabotropic glutamate 1/5 receptors (mGlu1/5R) are highly expressed in the hippocampus and the striatum of rodents and they are involved in behaviors regulated by these structures. We describe that H3R and mGlu1/5R crosstalk in pyramidal neurons of the hippocampus and in the striatum of rats. In addition, we found that signaling through H3R and mGlu1/5R were differently affected by chronic cocaine self-administration than the apparent crosstalk between the receptors.

    These results show evidence of GPCR interactions in adult rodent brain and reveal that chronic cocaine self-administration differently affected crosstalk and single receptor mediated signaling.