The novelty-seeking phenotype modulates the long-lasting effects of adolescent MDMA exposure

Rodrı́guez-Arias, Marta; Vaccaro, Sonia; Arenas, M. Carmen; Aguilar, M.A.; Miñarro, José

doi:10.1016/j.physbeh.2015.01.023

Cited by 13 publications

(12 citation statements)

References 78 publications

(116 reference statements)

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“…In particular, the hole-board test is a highly effective paradigm of novelty-seeking and predicts said sensitivity in adolescent male mice, since only high novelty seeker (HNS) adolescent mice have been shown to acquire the CPP induced by a low dose of cocaine, which is ineffective in inducing CPP in low novelty seeker (LNS) mice [ 42 ]. Moreover, we have observed a higher sensitivity of HNS to the conditioned rewarding effects of low doses of cocaine and MDMA in mice exposed to cocaine [ 43 ], ethanol [ 44 ], or MDMA [ 45 ]. However, the influence of the novelty-seeking phenotype on sensitivity to the rewarding effects of cannabinoids has not been studied to date.…”

Section: Introductionmentioning

confidence: 99%

Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait

et al. 2016

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Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP) induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS) in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p.) in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg), or cannabinoid antagonist rimonabant (1 mg/kg) and were subsequently conditioned with WIN 55212-2 (0.05 mg/kg, i.p.) or cocaine (1 or 6 mg/kg, i.p.). Only HNS mice conditioned with the 0.075 mg/kg dose acquired CPP with WIN 55212-2. Adolescent exposure to this cannabinoid agonist increased the rewarding effects of 1 mg/kg of cocaine in both HNS and LNS mice, and in HNS mice it also increased the reinstating effect of a low dose of cocaine. Our results endorse a role for individual differences such as a higher propensity for sensation-seeking in the development of addiction.

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Section: Introductionmentioning

confidence: 99%

Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait

et al. 2016

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“…For example, defeated mice were defined as high or low noveltyseeking (NS) according to their head-dip scores (below or above the defeated group median) in the hole board test. We have previously used this median-split analysis to study the effects of NS on the behavioral effects of different drugs of abuse (Arenas et al, 2014;Montagud-Romero et al, 2014;Mateos-García et al, 2015;Rodríguez-Arias et al, 2015, 2016. A one-way ANOVA with a between-subjects variable-Group, with three levels (Control, Defeated High Score and Defeated Low Score)-was performed for the following measures: time in defense/submission in the first episode of defeat, percentage of time in the open arms of the EPM, number of dips in the hole board, time of immobility in the TST, and grooming (frequency and time) in the splash test.…”

Section: Discussionmentioning

confidence: 99%

Behavioral Traits Associated With Resilience to the Effects of Repeated Social Defeat on Cocaine-Induced Conditioned Place Preference in Mice

Calpe-López

García-Pardo

Martínez-Caballero

et al. 2020

Front. Behav. Neurosci.

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The relationship between stress and drug use is well demonstrated. Stress-induced by repeated social defeat (RSD) enhances the conditioned place preference (CPP) induced by cocaine in mice. The phenomenon of resilience understood as the ability of subjects to overcome the negative effects of stress is the focus of increasing interest. Our aim is to characterize the behavior of resilient animals with respect to the effects of RSD on the CPP induced by cocaine. To this end, 25 male C57BL/6 mice were exposed to stress by RSD during late adolescence, while other 15 male mice did not undergo stress (controls). On the 2 days following the last defeat, all the animals carried out the elevated plus maze (EPM) and Hole Board, Social Interaction, Tail Suspension and Splash tests. Three weeks later, all the animals performed the CPP paradigm with a low dose of cocaine (1 mg/kg). Exposure to RSD decreased all measurements related to the open arms of the EPM. It also reduced social interaction, immobility in the tail suspension test (TST) and grooming in the splash test. RSD exposure also increased the sensitivity of the mice to the rewarding effects of cocaine, since only defeated animals acquired CPP. Several behavioral traits were related to resilience to the potentiating effect of RSD on cocaine CPP. Mice that showed less submission during defeat episodes, a lower percentage of time in the open arms of the EPM, low novelty-seeking, high social interaction, greater immobility in the TST and a higher frequency of grooming were those that were resilient to the long-term effects of social defeat on cocaine reward since they behaved like controls and did not develop CPP. These results suggest that the behavioral profile of resilient defeated mice is characterized by an active coping response during episodes of defeat, a greater concern for potential dangers, less reactivity in a situation of inevitable moderate stress and fewer depressive-like symptoms after stress. Determining the neurobehavioral substrates of resilience is the first step towards developing behavioral or pharmacological interventions that increase resilience in individuals at a high risk of suffering from stress.

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“…El CPL es un modelo basado en el aprendizaje clásico o pavloviano, para evaluar la recompensa condicionada inducida por diferentes estímulos (Bardo y Bevin, 2000;Tzschentke, 2007). Ha sido ampliamente utilizado para estudiar los efectos de recompensa de las drogas adictivas condicionadas (Aguilar, Rodríguez-Arias y Miñarro, 2009;Yap et al, 2015;Rodríguez-Arias et al, día et al 2017), ya que los estímulos contextuales pueden adquirir propiedades apetitivas secundarias cuando se combinan con un reforzador primario (Tzschentke, 2007). Para el CPL se emplearon 12 cajas idénticas de plexiglas con dos compartimentos de igual tamaño (30.7 cm de largo X 31.5 cm de ancho X 34.5 cm de alto), separadas por un área central de color gris (13.8 cm de largo X 31.5 cm de ancho X 34.5 cm de alto).…”

Section: Condicionamiento De La Preferencia De Lugarunclassified

“…Por lo tanto la exposición a una DS repetida induciría un incremento prolongado en el tiempo del valor motivacional de la cocaína incrementándose por tanto su potencial de abuso en los sujetos estresados. Nuestros resultados confirman numerosos estudios que han demostrado que la DS en ratones adolescentes y adultos, aumenta los efectos reforzantes de la cocaína utilizando el CPL (Arenas et al, 2016;Montagud-Romero et al, 2016a;Rodríguez-Arias et al, 2015, 2017Ferrer-Pérez et al, 2018a), o la autoadministración de cocaína (Boyson, Miguel, Quadros, DeBold y Miczek, 2011;Holly et al, 2016;Newman, Leonard, Arena, Almeida y Miczek, 2018;Arena, Covington, Herbert, DeBold y Miczek, 2019).…”

Section: Resiliencia Y Susceptibilidad Al Incremento De Los Efectos Runclassified

Caracterización conductual y neuroinmune de la resiliencia al estrés social: Efectos reforzantes de la cocaína

et al. 2020

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Numerosos estudios preclínicos han demostrado que el estrés social incrementa la vulnerabilidad a los efectos reforzantes de la cocaína. Sin embargo, los resultados obtenidos no son homogéneos, observándose siempre una subpoblación que no muestra dicho incremento. Utilizando el modelo de derrota social (DS) repetida en ratones, en este trabajo hemos querido caracterizar conductualmente a los ratones resilientes al incremento de los efectos reforzantes de la cocaína inducido por el estrés social. Utilizamos ratones adultos macho de la cepa C57/BL6 a los que sometimos al protocolo de DS repetida y tres semanas más tarde, realizamos el Condicionamiento de Preferencia de Lugar (CPL) inducido por una dosis no efectiva de cocaína (1mg/ kg). Una vez finalizado este procedimiento se midieron los niveles estriatales de interleucina 6, ya que el estrés social produce una respuesta de neuroinflamación. No se observó CPL en los ratones controles, pero los animales derrotados tomados en conjunto desarrollaron preferencia. Sin embargo, esta muestra se pudo dividir en ratones resilientes (no desarrollaron preferencia) y susceptibles (presentaron CPL). Durante las derrotas sociales, los animales resilientes pasaron menos tiempo en las conductas de huida y sumisión que los catalogados como susceptible y presentaron conductas de ataque hacia el ratón residente, manifestando por tanto resistencia a ser derrotados. No se observaron diferencias en la respuesta de neuroinflamación, probablemente debido al largo periodo de tiempo trascurrido desde la última derrota social. Nuestros resultados sugieren que un estilo de afrontamiento activo al estrés social va a ser determinante en la protección del sujeto a desarrollar un trastorno por uso de drogas.

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The novelty-seeking phenotype modulates the long-lasting effects of adolescent MDMA exposure

Cited by 13 publications

References 78 publications

Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait

Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait

Behavioral Traits Associated With Resilience to the Effects of Repeated Social Defeat on Cocaine-Induced Conditioned Place Preference in Mice

Caracterización conductual y neuroinmune de la resiliencia al estrés social: Efectos reforzantes de la cocaína

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