A reliable method to study cue-, priming-, and stress-induced reinstatement of cocaine self-administration in mice

Sòria, Guadalupe; Barbano, M. Flavia; Maldonado, Rafaël; Valverde, Olga

doi:10.1007/s00213-008-1184-x

Cited by 54 publications

(65 citation statements)

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(64 reference statements)

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“…Ventajas e inconvenientes de la AA. La popularidad de su uso radica en que este modelo cuenta con una excelente validez predictiva, ya que existe una gran similitud entre los resultados obtenidos con dicho modelo en animales y las conductas adictivas humanas (Koob et al, 2014;Mead, 2014;Schenk, 2009;Soria, Barbano, Maldonado y Valverde, 2008). Es decir, comparado con otros modelos de adicción, el paradigma de AA está muy relacionado con el abuso en humanos en cuanto a la forma de administración de la sustancia y a la respuesta conductual que se genera para conseguir la administración de la misma (O'Connor, Chapman, Butler y Mead, 2011).…”

Section: Modelos De Aprendizaje Operanteunclassified

“…La extinción hace referencia a un descenso progresivo en la respuesta operante asociada a la droga cuando esta sustancia no está presente (Epstein, Preston, Stewart y Shaham, 2006;Shaham, Shalev, Lu, de Wit y Stewart, 2003;Stewart, 2000). Después de la extinción, se da la fase de reinstauración de la conducta donde se mide la capacidad de ciertos estímulos (farmacológicos, físicos o ambientales) llamados "primers" para restablecer de nuevo la respuesta operante aprendida inicialmente (Soria et al, 2008). Actualmente, el modelo de extinción-reinstauración en AA es muy popular para modelar la recaída en la búsqueda de drogas (Bossert, Marchant, Calu y Shaham, 2013;Epstein et al, 2006;Shaham et al, 2003;Sinha et al, 2011;Soria et al, 2008 Recientemente, algunos estudios han evaluado los efectos de desestabilizar el recuerdo de lo que los animales han aprendido durante la adquisición de la AA mediante procedimientos conductuales (extinción) o farmacológicos.…”

Section: Modelos De Aprendizaje Operanteunclassified

“…Después de la extinción, se da la fase de reinstauración de la conducta donde se mide la capacidad de ciertos estímulos (farmacológicos, físicos o ambientales) llamados "primers" para restablecer de nuevo la respuesta operante aprendida inicialmente (Soria et al, 2008). Actualmente, el modelo de extinción-reinstauración en AA es muy popular para modelar la recaída en la búsqueda de drogas (Bossert, Marchant, Calu y Shaham, 2013;Epstein et al, 2006;Shaham et al, 2003;Sinha et al, 2011;Soria et al, 2008 Recientemente, algunos estudios han evaluado los efectos de desestabilizar el recuerdo de lo que los animales han aprendido durante la adquisición de la AA mediante procedimientos conductuales (extinción) o farmacológicos. En estos estudios, tras conseguir una adquisición estable de la AA, se reactiva la memoria (exponiendo a los animales a la caja de AA durante un breve intervalo de tiempo) y poco tiempo después (de minutos a un par de horas), los animales realizan sesiones de extinción o reciben una inyección de un fármaco amnésico.…”

Section: Modelos De Aprendizaje Operanteunclassified

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Modelos animales de adicción a las drogas

et al. 2017

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Resumen Abstract adicciones vol. 29, nº 4 · 2017 revisión Modelos animales de adicción a las drogas Animal Models of Drug AddictionMaría Pilar García Pardo*,**; Concepción Roger Sánchez*; José Enrique de la Rubia Ortí**; María Asunción Aguilar Calpe*. En los últimos años los modelos han incorporado modificaciones metodológicas para incluir el estudio de los procesos de extinción, reinstauración y reconsolidación o para modelar aspectos concretos de la conducta adictiva como puede ser la motivación para consumir la droga, el consumo compulsivo o la búsqueda de la droga bajo situaciones de castigo. Otros modelos interrelacionan diferentes componentes del refuerzo o modelan la motivación voluntaria por consumir (modelos de "two-bottle choice" o "drinking in the dark").En definitiva, las innovaciones en estos modelos contribuyen al avance en el conocimiento científico de los diferentes factores que llevan a tomar una droga y a desarrollar un consumo compulsivo, ofreciendo una vía para identificar futuros tratamientos para la adicción.Palabras clave: Refuerzo; Adicción; Modelos animales; Drogas de abuso.

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Section: Modelos De Aprendizaje Operanteunclassified

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Modelos animales de adicción a las drogas

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“…The repeated cycles of relapse after cessation of consumption remain the major clinical concern in the treatment of drug addiction (Miller and Gold, 1994;Weiss, 2010). In our laboratory, we have recently validated novel models of reinstatement of drug and food-seeking behavior (MartinGarcia et al, 2011;Soria et al, 2008) in mice that allow to study the neurobiological mechanisms of relapse through the use of genetically modified mice.…”

Section: Introductionmentioning

confidence: 99%

Effects of Genetic Deletion of Endogenous Opioid System Components on the Reinstatement of Cocaine-Seeking Behavior in Mice

Gutiérrez‐Cuesta

Burokas

Mancino

et al. 2014

Neuropsychopharmacol

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The repeated cycles of cessation of consumption and relapse remain the major clinical concern in treating drug addiction. The endogenous opioid system is a crucial component of the reward circuit that participates in the adaptive changes leading to relapse in the addictive processes. We have used genetically modified mice to evaluate the involvement of m-opioid receptor (MOR) and d-opioid receptor (DOR) and their main endogenous ligands, the enkephalins derived from proenkephalin (PENK) and prodynorphin (PDYN), in the reinstatement of cocaine-seeking behavior. Constitutive knockout mice of MOR, DOR, PENK, and PDYN, and their wild-type littermates were trained to self-administer cocaine or to seek for palatable food, followed by a period of extinction and finally tested on a cue-induced reinstatement of seeking behavior. The four lines of knockout mice acquired operant cocaine self-administration behavior, although DOR and PENK knockout mice showed less motivation for cocaine than wild-type littermates. Moreover, cue-induced relapse was significantly decreased in MOR and DOR knockout mice. In contrast, PDYN knockout mice showed a slower extinction and increased relapse than wild-type littermates. C-Fos expression analysis revealed differential activation in brain areas related with memory and reward in these knockout mice. No differences were found in any of the four genotypes in operant responding to obtain palatable food, indicating that the changes revealed in knockout mice were not due to unspecific deficit in operant performance. Our results indicate that MOR, DOR, and PDYN have a differential role in cue-induced reinstatement of cocaine-seeking behavior.

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“…Nicotine self-administration sessions were performed in accordance to protocols previously described (Burokas et al, 2012;Martin-Garcia et al, 2009;Soria et al, 2008;Soria et al, 2005). Details of the apparatus, surgery, and the nicotine self-administration procedure are included in the Supplementary Information.…”

Section: Intravenous Nicotine Self-administrationmentioning

confidence: 99%

Role of CB2 Cannabinoid Receptors in the Rewarding, Reinforcing, and Physical Effects of Nicotine

Navarrete

Rodrı́guez-Arias

Martín‐García

et al. 2013

Neuropsychopharmacol

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This study was aimed to evaluate the involvement of CB2 cannabinoid receptors (CB2r) in the rewarding, reinforcing and motivational effects of nicotine. Conditioned place preference (CPP) and intravenous self-administration experiments were carried out in knockout mice lacking CB2r (CB2KO) and wild-type (WT) littermates treated with the CB2r antagonist AM630 (1 and 3 mg/kg). Gene expression analyses of tyrosine hydroxylase (TH) and a3-and a4-nicotinic acetylcholine receptor subunits (nAChRs) in the ventral tegmental area (VTA) and immunohistochemical studies to elucidate whether CB2r colocalized with a3-and a4-nAChRs in the nucleus accumbens and VTA were performed. Mecamylamine-precipitated withdrawal syndrome after chronic nicotine exposure was evaluated in CB2KO mice and WT mice treated with AM630 (1 and 3 mg/kg). CB2KO mice did not show nicotine-induced place conditioning and selfadministered significantly less nicotine. In addition, AM630 was able to block (3 mg/kg) nicotine-induced CPP and reduce (1 and 3 mg/kg) nicotine self-administration. Under baseline conditions, TH, a3-nAChR, and a4-nAChR mRNA levels in the VTA of CB2KO mice were significantly lower compared with WT mice. Confocal microscopy images revealed that CB2r colocalized with a3-and a4-nAChRs. Somatic signs of nicotine withdrawal (rearings, groomings, scratches, teeth chattering, and body tremors) increased significantly in WT but were absent in CB2KO mice. Interestingly, the administration of AM630 blocked the nicotine withdrawal syndrome and failed to alter basal behavior in saline-treated WT mice. These results suggest that CB2r play a relevant role in the rewarding, reinforcing, and motivational effects of nicotine. Pharmacological manipulation of this receptor deserves further consideration as a potential new valuable target for the treatment of nicotine dependence.

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A reliable method to study cue-, priming-, and stress-induced reinstatement of cocaine self-administration in mice

Abstract: The effective reinstatement model that we have developed will become a useful tool for future understanding of the neurobiological basis of cocaine addiction and relapse, specifically, with the use of genetically modified mice.

Cited by 54 publications

References 50 publications

Modelos animales de adicción a las drogas

Modelos animales de adicción a las drogas

Effects of Genetic Deletion of Endogenous Opioid System Components on the Reinstatement of Cocaine-Seeking Behavior in Mice

Role of CB2 Cannabinoid Receptors in the Rewarding, Reinforcing, and Physical Effects of Nicotine

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