Cannabidiol as a potential therapeutic strategy to reduce cocaine seeking in mice

• Autores: Miguel Á. Luján Pérez
• Directores de la Tesis: Olga Valverde Granados (dir. tes.)
• Lectura: En la Universitat Pompeu Fabra ( España ) en 2020
• Idioma: español
• Tribunal Calificador de la Tesis: Mercé Correa (presid.), Francina Fonseca Casals (secret.), Vincent Vialou (voc.)
• Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
• Materias:
  • Psicología
    • Psicología experimental
      • Análisis experimental de la conducta
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • Cocaine addiction is a chronic, relapsing disease characterized by the compulsive seeking and use of the drug despite its harmful consequences. Currently, there are no approved pharmacotherapies available for the treatment of cocaine addiction. Recently, isolated phytocannabinoid products have drawn great attention due to its potential therapeutic applications in diverse psychiatric conditions, including drug addiction. For instance, cannabidiol, unlike Δ9-tetrahydrocannabinol, does not directly activate cannabinoid receptors and thus, it is devoid of adverse, reinforcing effects. Moreover, pre-clinical and clinical studies suggest that cannabidiol could reduce the behavioral and molecular manifestations of maladaptive neuroplasticity underlying drug addiction. Here, we sought to determine the motivational effects of a subchronic treatment of cannabidiol in CD-1 male mice exposed to a volitional paradigm of cocaine operant intake. Cannabidiol treatment reduces certain behavioral manifestations of cocaine reinforcement while showing anxiolytic and cognitive benefits. Behavioral effects are associated to attenuated cocaine-induced conditioned place preference, decreased total cocaine intake, reduced cocaine seeking under a reinforcement schedule of progressive ratio and diminished cue-induced reinstatement of cocaine seeking behavior. Noteworthy, not all measures of cocaine reinforcement ameliorate after cannabidiol repeated treatment. Furthermore, pharmacological approximations to the responsible mechanisms of action reveal a crucial role of cannabidiol’s pro-neurogenic effects in the attenuation of cocaine voluntary intake. The differential effects of cannabidiol treatment in reinstatement conditions are probably regulated by CB1 receptor-dependent activity. Altogether, our results expand upon the evidence supporting that cannabidiol has a protective, but limited, influence on the neurobehavioral development and expression of cocaine operant seeking and intake.