Rodents housed with a running wheel can exhibit attenuated cocaine seeking and cocaine-induced psychomotor activation. However, the longevity of such a protection and the influence of the developmental stage during which exercise is displayed received little attention. Here, females and males C57BL/6J mice, aged 28 (adolescents) or 77 (adults) days were housed with (n = 56) or without (n = 28) a running wheel. After 3 weeks in these conditions, half of the exercised mice were deprived of their wheel (n = 28) whereas the other half and the sedentary mice were kept in their respective environments. After 3 additional weeks, mice were tested for initiation of psychomotor sensitization to 9 once-daily intraperitoneal injections of 8 mg/kg cocaine (following 2 drug-free sessions). The expression of sensitization was assessed on a single session 30 days after the last cocaine injection. Continuously exercised mice (wheel throughout experimentation) were less responsive to the initiation and the expression of cocaine effects, regardless of the gender and the developmental period during which exercise was introduced. A 3-week regimen of wheel-running exercise during adolescence (from 28 to 50 days of age) attenuated in later life the initiation and the expression of sensitization in females and its expression in males. In contrast, females and males previously exercised as adults (from 77 to 99 days of age) and their corresponding sedentary counterparts exhibited indiscernible levels of initiation and expression of sensitization. These results suggest that early-life period such as adolescence may be particularly sensitive to the long-term protection of exercise against cocaine vulnerability.

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Despite substantial health benefits, smoking cessation attempts have high relapse rates. Neuroimaging measures can sometimes predict individual differences in substance use phenotypes – including relapse – better than behavioral metrics alone. No study to date has compared the relative prediction ability of changes in psychological processes across prolonged abstinence with corresponding changes in brain activity. Here, in a longitudinal design, measurements were made one day prior to smoking cessation, and at 1 and 4 weeks post-cessation (total n=120). Next, we tested the relative role of changes in psychosocial variables vs. task-based functional brain measures predicting time to nicotine relapse up to 12 months. Abstinence was bioverified 4-5 times during the first month. Data were analyzed with a novel machine learning approach to predict relapse. Results showed that increased electrophysiological brain activity during inhibitory control predicted longer time-to-relapse (c-index=0.56). However, reward-related brain activity was not predictive (c-index=0.45). Psychological variables, notably an increase during abstinence in psychological flexibility when experiencing negative smoking-related sensations, predicted longer time-to-relapse (c-index=0.63). A model combining psychosocial and brain data was predictive (c-index=0.68). Using a best-practice approach, we demonstrated generalizability of the combined model on a previously unseen holdout validation dataset (c-index=0.59 vs. 0.42 for a null model). These results show that changes during abstinence – increased smoking-specific psychological flexibility and increased inhibitory control brain function – are important in predicting time to relapse from smoking cessation. In the future, monitoring and augmenting changes in these variables could help improve the chances of successful nicotine smoking abstinence.

While animal research has consistently reported preventive effects of exercise against drug abuse vulnerability, little is known about the influence of the developmental stage during which exercise is displayed on addictive drugs responsiveness. This study aimed to determine whether prenatal exercise could attenuate acute cocaine reactivity and psychomotor sensitization in youth offspring. We used a split-plot factorial design where C57BL/6J females were randomly assigned into sedentary or exercised (wheel-running) conditions before and during gestation, the wheels being removed on gestational day 18.Offspring were weaned, gendered and individually housed on 24-28 days old. At 38-42 days old, they were tested for their acute psychomotor responsiveness to 8 mg/kg cocaine and their initiation of sensitization over 8 additional once-daily administrations, the long-term expression of sensitization occurring 30 days later. Adolescent females born from exercised mothers were much less responsive to the acute psychomotor-stimulating effect of cocaine than those born from sedentary mothers (d = 0.75, p = .02), whereas there was no evidence for such a difference in males (d = 0.34, p = .17). However, we did not find sizeable attenuating effects of prenatal exercise on the initiation and the long-term expression of the psychomotor-activating effect of cocaine, in either sex (Cohen's ds varying from -0.23 to 0.39). These results suggest that prenatal exercise may induce initial protection against cocaine responsiveness in youth females, a finding that warrants further research.

While animal research has consistently reported preventive effects of exercise against drug abuse vulnerability, little is known about the influence of the developmental stage during which exercise is displayed on addictive drugs responsiveness. This study aimed to determine whether prenatal exercise could attenuate acute cocaine reactivity and psychomotor sensitization in youth offspring. We used a split-plot factorial design where C57BL/6J females were randomly assigned into sedentary or exercised (wheel-running) conditions before and during gestation, the wheels being removed on gestational day 18.Offspring were weaned, gendered and individually housed on 24-28 days old. At 38-42 days old, they were tested for their acute psychomotor responsiveness to 8 mg/kg cocaine and their initiation of sensitization over 8 additional once-daily administrations, the long-term expression of sensitization occurring 30 days later. Adolescent females born from exercised mothers were much less responsive to the acute psychomotor-stimulating effect of cocaine than those born from sedentary mothers (d = 0.75, p = .02), whereas there was no evidence for such a difference in males (d = 0.34, p = .17). However, we did not find sizeable attenuating effects of prenatal exercise on the initiation and the long-term expression of the psychomotor-activating effect of cocaine, in either sex (Cohen's ds varying from -0.23 to 0.39). These results suggest that prenatal exercise may induce initial protection against cocaine responsiveness in youth females, a finding that warrants further research.

Caring for a relative with a severe mental disorder puts family caregivers to a great risk of depression. While overall caregiving burden is a strong predictor of depression, the contribution of the various dimensions of burden to caregivers’ depression as well as their relationships with depressive symptoms has received little attention. 384 family caregivers completed a cross-sectional online survey including the Center for Epidemiological Studies Depression (CES-D) scale, the Zarit Burden Interview (ZBI), and the Brief Experience of Caregiving Inventory (BECI), measuring caregiving burden and experience. We estimated the structure of the relationships between caregiving experiences (i.e., ZBI and BECI subscales) and CES-D symptoms using a network approach. Negative Emotion/Consequences, (lack of) Positive Personal Experience, and Stigma/Effects on Family were the most connected caregiving dimensions to depression. To untangle the role of the Negative Emotion/Consequences component (by far the most central node in estimated networks), a secondary analysis incorporating its composing items was estimated. Losing control over life, feeling strained around the relative and impaired self-perceived health emerged as central nodes. Interestingly, these caregiving-related dimensions or experiences were differentially connected to depressive symptoms. We discuss how these findings might help future research and inform tailored psychoeducational interventions for family caregivers of people with a severe mental disorder.

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