Neuroactivational and Behavioral Correlates of Psychosocial Stress-Induced Cocaine Seeking in Rats

A prominent feature of cocaine abuse is a high risk of relapse even despite prolonged periods of abstinence. Psychosocial stress is thought to be a major contributor to the onset of cocaine craving and relapse in human substance abusers, yet most preclinical models of stress-induced relapse employ physical stressors (e.g., unpredictable footshock) or pharmacological stressors (e.g., yohimbine to elicit a drug seeking response) and do not rely upon psychosocial stress per se. Importantly, social stressors are well known to activate distinct neural circuits within the brain as compared to other stressors. It is therefore possible that currently available animal models of stress-induced drug relapse do not fully engage the neuroanatomical, neurochemical, and/or molecular substrates that are recruited specifically by psychosocial stressors to produce drug-seeking behavior. Social defeat stress has been proposed as an ethologically valid psychosocial stressor in rodents that more closely models the forms of psychosocial stress that precede relapse episodes in drug abusers. We previously developed a model of psychosocial stress-induced reinstatement in rats in which cocaine seeking is elicited via exposure to a cue signaling impending social defeat stress. Using this model, we discovered that predilection towards displaying active coping behaviors during prior social defeat stress exposures was positively correlated with levels of psychosocial stress-induced cocaine seeking. The present study aimed to expand upon these initial findings by assessing and comparing patterns of neural activation in key brain areas during stress induced cocaine seeking that is triggered by psychosocial or footshock stress predictive cues

Predictive Ability of Pressure-Corrected Arterial Stiffness Indices:Comparison of Pulse Wave Velocity, Cardio-Ankle Vascular Index (CAVI), and CAVI0

BACKGROUND: Pulse wave velocity (PWV) is blood pressure (BP) dependent, leading to the development of the BP-corrected metrics cardio-ankle vascular index (CAVI) and CAVI(0). We aimed to assess risk prediction by heart-to-ankle PWV (haPWV), CAVI, and CAVI(0) in a US population. METHODS: We included 154 subjects (94.8% male; 47.7% African American) with and without heart failure (HF). Left and right haPWV, CAVI, and CAVI(0) were measured with the VaSera 1500N device. We prospectively followed participants for a mean of 2.56 years for the composite endpoint death or HF-related hospital admission (DHFA). RESULTS: Left and right haPWV, CAVI, and CAVI(0) values did not differ significantly. In unadjusted analyses, haPWV (left standardized hazard ratio [HR] = 1.51, P = 0.007; right HR = 1.66, P = 0.003), CAVI (left HR = 1.45, P = 0.012; right HR = 1.58, P = 0.006), and CAVI(0) (left HR = 1.39, P = 0.022; right HR = 1.44, P = 0.014) significantly predicted DHFA. Predictive ability showed a decreasing trend from haPWV to CAVI to CAVI(0); in line with the increasing amount of BP correction in these metrics. In Cox models, right-sided metrics showed a trend toward stronger predictive ability than left-sided metrics. After adjustment for baseline HF status, the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, and systolic BP, right haPWV (HR = 1.58, P = 0.025) and CAVI (HR = 1.44, P = 0.044), but no other stiffness metrics, remained predictive. CONCLUSIONS: Although conceptually attractive, BP-corrected arterial stiffness metrics do not offer better prediction of DHFA than conventional arterial stiffness metrics, nor do they predict DHFA independently of systolic BP. Our findings support PWV as the primary arterial stiffness metric for outcome prediction