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Activation of neurotensin receptor type 1 attenuates locomotor activity.
Vadnie, Chelsea A; Hinton, David J; Choi, Sun; Choi, YuBin; Ruby, Christina L; Oliveros, Alfredo; Prieto, Miguel L; Park, Jun Hyun; Choi, Doo-Sup.
Afiliación
  • Vadnie CA; Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Hinton DJ; Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Choi S; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Choi Y; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Ruby CL; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Oliveros A; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Prieto ML; Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Universidad de los Andes, Facultad de Medicina, Departamento de Psiquiatría, Santiago, Chile.
  • Park JH; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Choi DS; Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochest
Neuropharmacology ; 85: 482-92, 2014 Oct.
Article en En | MEDLINE | ID: mdl-24929110
Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF-81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neurotensina / Fármacos del Sistema Nervioso Central / Corteza Prefrontal / Receptores de Neurotensina / Actividad Motora / Núcleo Accumbens Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neurotensina / Fármacos del Sistema Nervioso Central / Corteza Prefrontal / Receptores de Neurotensina / Actividad Motora / Núcleo Accumbens Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido