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

Abstract

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.

Voluntary wheel running protects against the increase in ethanol consumption induced by social stress in mice

“…In the present study, we have observed that those animals that spent more time in avoidance and flee behaviors during the last SD presented higher EtOH intake. We have obtained similar results in a previous study (Ródenas-González et al, 2020), where we observed a positive correlation between flight and avoidance behaviors and the increase in the conditioned rewarding effects of cocaine in the CPP. These results confirm that active coping and adequate adaptation to stress reduces the increase in the rewarding effects of drugs of abuse induced by social stress.…”

CB2 agonist mitigates cocaine-induced reinstatement of place preference and modulates the inflammatory response in mice

“…In our experiments, cocaine produced a robust preference for the drug-paired compartment and, at a lower dose, evoked reinstatement of CPP after extinction, corroborating earlier studies (Shippenberg and Heidbreder, 1995; Ródenas-González et al ., 2021). Cocaine-induced CPP reinstatement was inhibited by JWH-133 at a dose of 10 mg/kg which abolished both chamber preference and cocaine-induced locomotor activity.…”

Neuroinflammatory and behavioral susceptibility profile of mice exposed to social stress towards cocaine effects

“…Moreover, mice that are resilient to develop anxiety when exposed to odor of a depredator exhibit changes in their dopaminergic system, suggesting a particular response of these animals to cocaine (Brodnik et al, 2017). In a previous study, we report that mice resilient to stress-induced increases in cocaine reward display less flee and avoidance behaviors during the intruder-resident encounter (Ródenas-González et al, 2020). The results of the present study confirm once again that susceptible mice adopt a passive-reactive coping profile during social defeat encounters, employing more time in flee/avoidance and submissive/defensive behaviors during the social defeat than those categorized as resilient.…”

“…We have previously shown that depending on their response to cocaine-conditioned effects, there are two different populations among the defeated mice (Ródenas-González et al, 2020). In that study, we showed that three weeks after the last episode of social stress, a susceptible group of mice showed a place preference for a sub-threshold dose of cocaine as a result of an increased response to cocaine.…”