Social defeat stress and escalation of cocaine and alcohol consumption: Focus on CRF

Newman, Emily L.; Leonard, Michael Z.; Arena, Danielle T.; Almeida, Rosa M. M. de; Miczek, Klaus A.

doi:10.1016/j.ynstr.2018.09.007

Cited by 53 publications

(41 citation statements)

References 260 publications

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“…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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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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“…A particularly effective social stress model in rodents is the resident-intruder social defeat model in which mice are repeatedly exposed to an unfamiliar, dominant aggressor (Newman et al, 2018) and either socialize with this intruder (where the mice are then dubbed “resilient”) or become anti-social (and are considered more “susceptible” to trauma). This distinction is then used to study biological markers of trauma in the susceptible population.…”

Section: Animal Models Of Ptsdmentioning

confidence: 99%

“…Despite altered activity of the BNST following social defeat, pCREB and pERK expression were unchanged (although perhaps these markers are not activated by social stimuli; Trainor et al, 2011). Finally, intermittent episodes of social stress escalate alcohol and cocaine intake in rats, but continuous exposure attenuates cocaine intake and increases alcohol intake (Newman et al, 2018), a behavioral change that may (like other models of stress-induced reinstatement to drug-seeking; see Miles et al, 2018) be BNST-dependent. Because BNST activity may drive PTSD-like symptomology, neurochemical and anatomical alterations after social defeat stress suggest a critical involvement of BNST in the maintenance and development of PTSD.…”

Section: Animal Models Of Ptsdmentioning

confidence: 99%

Role of the Bed Nucleus of the Stria Terminalis in PTSD: Insights From Preclinical Models

Miles

Maren

2019

Front. Behav. Neurosci.

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Post-traumatic stress disorder (PTSD) afflicts approximately 8% of the United States population and represents a significant public health burden, but the underlying neural mechanisms of this and other anxiety- and stressor-related disorders are largely unknown. Within the last few decades, several preclinical models of PSTD have been developed to help elucidate the mechanisms underlying dysregulated fear states. One brain area that has emerged as a critical mediator of stress-related behavioral processing in both clinical and laboratory settings is the bed nucleus of the stria terminalis (BNST). The BNST is interconnected with essential emotional processing regions, including prefrontal cortex, hippocampus and amygdala. It is activated by stressor exposure and undergoes neurochemical and morphological alterations as a result of stressor exposure. Stress-related neuro-peptides including corticotropin-releasing factor (CRF) and pituitary adenylate cyclase activating peptide (PACAP) are also abundant in the BNST, further implicating an involvement of BNST in stress responses. Behaviorally, the BNST is critical for acquisition and expression of fear and is well positioned to regulate fear relapse after periods of extinction. Here, we consider the role of the BNST in stress and memory processes in the context of preclinical models of PTSD.

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“…Brief episodes of aggression from a more aggressive conspecific, together with social subordination, induce anxiety-and depression-like symptoms (Bartolomucci et al, 2009;Nestler and Hyman, 2010;Hollis and Kabbaj, 2014;Czéh et al, 2016;Vannan et al, 2018). Exposure to RSD has also been shown to increase the rewarding effects of drugs of abuse (Ellenbroek et al, 2005;Burke et al, 2011;Aguilar et al, 2013;García-Pardo et al, 2015Newman et al, 2018). Moreover, several studies performed in our laboratory using the conditioned place preference (CPP) paradigm have demonstrated that mice exposed to RSD during late adolescence exhibit an enhanced sensitivity to the rewarding effects of low doses of cocaine in adulthood (Montagud-Romero et al, 2016a,b;Rodríguez-Arias et al, 2017;García-Pardo et al, 2019).…”

Section: Introductionmentioning

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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Social defeat stress and escalation of cocaine and alcohol consumption: Focus on CRF

Cited by 53 publications

References 260 publications

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

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

Role of the Bed Nucleus of the Stria Terminalis in PTSD: Insights From Preclinical Models

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

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