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

Abstract

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.

Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol

“…Locomotor activity is a commonly used physiological characteristic that reflects whether the central nervous system is excited or inhibited, sedative hypnotics such as diazepam can significantly reduce the locomotor activity of rats (Mendez-Cuesta et al, 2011), and stimulants of the central nervous system such as caffeine can increase the locomotor activity of rats (Alsufyani and Docherty, 2017). Conditional place preference test is a commonly used method to evaluate the dependence potential of drugs (Calpe-Lopez et al, 2019). This is our first attempt to use facial reactivity scale to examine the hedonic effects of propofol.…”

Roles of Oxytocin in Stress Responses, Allostasis and Resilience

“…Telomere length has been shown to be increased by social enrichment via oxytocin signaling, suggesting that oxytocin induced by social enrichment has an anti-aging effect [ 169 ]. In oxytocin receptor-deficient mice, an increase in defeat posturing during second social defeat stress by repeated social defeat stress was not observed [ 11 ], suggesting that oxytocin facilitates active coping behaviors in response to repeated stressors to confer resilience [ 170 , 171 ].…”

Drug-Induced Conditioned Place Preference and Its Practical Use in Substance Use Disorder Research

“…Therefore, it is more accurate to state that reinstatement in CPP more directly reflects a continuation of CPP behaviors, whether it be triggered by a drug-prime injection or a stressor. Types of stressors that have been utilized to trigger reinstatement include: (1) naturalistic stressors, such as water/food deprivation, physical restraint stress (Ribeiro Do Couto et al, 2006 ), painful stimuli such as the foot-shock paradigm (Wang et al, 2000 ; Sanchez and Sorg, 2001 ), and fear/anxiety-inducing stimuli such as the forced swim stress (Sanchez and Sorg, 2001 ; Ribeiro Do Couto et al, 2006 ; Redila and Chavkin, 2008 ); (2) social disruption/conflict stressors including social isolation and maternal deprivation (Ribeiro Do Couto et al, 2006 ; Calpe-López et al, 2020 ); and (3) pharmacological stressors, such as injections of agonists of the kappa opioid system (Redila and Chavkin, 2008 ), and yohimbine (Mantsch et al, 2010 ). While comparisons of drug-prime vs. stressor-induced reinstatement models are common concerning operant drug self-administration paradigms, they are rather limited in the field of CPP (Mantsch et al, 2016 ).…”