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Intra-ventral tegmental area microinjections of urotensin II modulate the effects of cocaine.
Mueller, L E; Kausch, M A; Markovic, T; MacLaren, D A A; Dietz, D M; Park, J; Clark, S D.
Afiliación
  • Mueller LE; Department of Pharmacology and Toxicology, State University of New York at Buffalo, NY 14214, USA.
  • Kausch MA; Department of Pharmacology and Toxicology, State University of New York at Buffalo, NY 14214, USA.
  • Markovic T; Department of Pharmacology and Toxicology, State University of New York at Buffalo, NY 14214, USA.
  • MacLaren DA; Department of Pharmacology and Toxicology, State University of New York at Buffalo, NY 14214, USA.
  • Dietz DM; Department of Pharmacology and Toxicology, State University of New York at Buffalo, NY 14214, USA; Research Institute on Addictions, State University of New York at Buffalo, NY 14214, USA.
  • Park J; Department of Biotechnology and Clinical Laboratory Sciences, State University of New York at Buffalo, NY 14214, USA.
  • Clark SD; Department of Pharmacology and Toxicology, State University of New York at Buffalo, NY 14214, USA; Department of Psychology, State University of New York at Buffalo, NY 14214, USA; Research Institute on Addictions, State University of New York at Buffalo, NY 14214, USA. Electronic address: stewartc@
Behav Brain Res ; 278: 271-9, 2015 Feb 01.
Article en En | MEDLINE | ID: mdl-25264578
Although the peptide urotensin II (UII) has well studied direct actions on the cardiovascular system, the UII receptor (UIIR) is expressed by neurons of the hindbrain. Specifically, the UIIR is expressed by the cholinergic neurons of the laterodorsal tegmentum (LDTg) and the pedunculopontine tegmentum (PPTg). These neurons send axons to the ventral tegmental area (VTA), for which the PPTg and LDTg are the sole source of acetylcholine. Therefore, it was hypothesized that UIIR activation within the VTA would modulate reward-related behaviors, such as cocaine-induced drug seeking. Intra-VTA microinjections of UII at high concentrations (1 nmole) established conditioned place preference (CPP), but also blocked cocaine-mediated CPP (10 mg/kg). When rats received systemic sub-effectual doses of cocaine (7.5 mg/kg) with intra-VTA injections of 1 or 10 pmole of UII CPP was formed. Furthermore, the second endogenous ligand for the UIIR, urotensin II-related peptide, had the same effect at the 10 pmole dose. The effects of low doses of UII were blocked by pretreatment with the UIIR antagonist SB657510. Furthermore, it was found that intra-VTA UII (10 pmole) further increased cocaine-mediated (7.5 mg/kg) rises in electrically evoked dopamine in the nucleus accumbens. Our study has found that activation of VTA-resident UIIR produces observable behavioral changes in rats, and that UIIR is able to modulate the effects of cocaine. In addition, it was found that UIIR activation within the VTA can potentiate cocaine-mediated neurochemical effects. Therefore, the coincident activation of the UII-system and cocaine administration may increase the liability for drug taking behavior.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Urotensinas / Cocaína / Área Tegmental Ventral / Receptores Acoplados a Proteínas G / Comportamiento de Búsqueda de Drogas Límite: Animals Idioma: En Revista: Behav Brain Res Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Urotensinas / Cocaína / Área Tegmental Ventral / Receptores Acoplados a Proteínas G / Comportamiento de Búsqueda de Drogas Límite: Animals Idioma: En Revista: Behav Brain Res Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos