Study Protocol: Effect of prenatal wheel-running exercise (before and during gestation) on cocaine psychomotor sensitization expressed in the offspring in periadolescent females and males C57BL/6J mice

The present study principally aims at determining to which extent prenatal exercise (before and during gestation) could affect the initiation (establishment) and the expression of psychomotor sensitization induced by a representative dose of cocaine in young female and male mice. More specifically, we will assess cocaine-induced acute psychomotor-activating effects, psychomotor sensitization developing over 9 daily sessions (daily peritoneal injections of cocaine or saline) and the long-term expression of the sensitized response (30 days after the last sensitizing injection) in C57BL/6J mice born from mothers housed with or without a running wheel before and during gestation. Based on literature and on our prior results, the mice born from exercised mothers are expected to show significantly reduced levels of cocaine responsiveness in comparison with the control mice (born from unexercised mothers)

Network analysis of the associations between personality traits, cognitive functioning, and inflammatory markers in elderly individuals without dementia

IntroductionLower cognitive functioning in old age has been associated with personality traits or systemic inflammatory markers. Associations have also been found between personality traits and inflammatory markers. However, no study has explored the inter-relationships between these three components simultaneously. The present study aims to better understand the inter-relationships among personality traits, inflammatory markers, and cognitive performance in elderly individuals without dementia.MethodsThis study utilizes a network analysis approach, a statistical method that allows visualization of the data’s unique pairwise associations. We performed a cross-sectional analysis on 720 elderly individuals without dementia, using data from Colaus|PsyColaus, a population-based study conducted in Lausanne, Switzerland. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to assess personality traits, and interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were used as peripheral inflammatory markers. Cognitive domains were investigated using the Mini-Mental State Examination (MMSE), the Verbal Fluency Test, the Stroop Test, the DO40, and the Free and Cued Selective Reminding (FCSR) test.ResultsOpenness was associated with verbal fluency and Agreeableness with immediate free recall. In contrast, no association between inflammatory markers and personality traits or cognition was identified.DiscussionIn elderly individuals without dementia, a high level of Openness or Agreeableness was associated with executive functioning/semantic memory and episodic memory, respectively

Front Aging Neurosci

INTRODUCTION: Lower cognitive functioning in old age has been associated with personality traits or systemic inflammatory markers. Associations have also been found between personality traits and inflammatory markers. However, no study has explored the inter-relationships between these three components simultaneously. The present study aims to better understand the inter-relationships among personality traits, inflammatory markers, and cognitive performance in elderly individuals without dementia. METHODS: This study utilizes a network analysis approach, a statistical method that allows visualization of the data's unique pairwise associations. We performed a cross-sectional analysis on 720 elderly individuals without dementia, using data from Colaus|PsyColaus, a population-based study conducted in Lausanne, Switzerland. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to assess personality traits, and interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were used as peripheral inflammatory markers. Cognitive domains were investigated using the Mini-Mental State Examination (MMSE), the Verbal Fluency Test, the Stroop Test, the DO40, and the Free and Cued Selective Reminding (FCSR) test. RESULTS: Openness was associated with verbal fluency and Agreeableness with immediate free recall. In contrast, no association between inflammatory markers and personality traits or cognition was identified. DISCUSSION: In elderly individuals without dementia, a high level of Openness or Agreeableness was associated with executive functioning/semantic memory and episodic memory, respectively

Wheel-running exercise during adolescence does not substantially affect cocaine conditioned place preference in male C57BL/6J mice

Epidemiological studies suggest that physical exercise could have preventive properties against drugs of abuse vulnerability. Animal research showed that rats or mice housed with a running wheel (a model of aerobic exercise) can exhibit attenuated drug self-administration or drug-induced psychomotor hyperactivity in comparison with their sedentary counterparts. However, the few experiments using conditioned place preference (CPP) are conflicting (positive, negative or null effects of exercise). Aspects or deficiencies of the methods used in some studies, in particular the low sample size (median n=8), the absence of a baseline pre-conditioning session or a control group in the design or (when present) in the data analyses, make the whole picture of results difficult to understand, a situation which warrants further studies, possibly of a better quality than the previous ones. Objectives. Our purpose was to test whether wheel-running exercise during adolescence could impact the formation and long-term retention of CPP to cocaine in mice. Method. Male C57BL/6J mice were individually housed either with (n=32) or without (n=32) a running wheel from 35 days of age. Behavioral testing begun 3 weeks after such housing, all animals being first tested under saline for their baseline preference (white or black compartments). Then, mice underwent 10 once-daily conditioning sessions receiving peritoneal injections of 10 mg/kg cocaine and saline on alternate days (n=16). The white compartment (always non-preferred) was systematically associated to cocaine effects. Control mice received saline every day (n=16). One and 21 days after the last conditioning session, mice were tested for place preference under saline. CPP scores were analyzed with a priori single (cocaine vs saline) and crossed contrasts (testing the housing-by-drug interaction). Each contrast (t-test) incorporated the mean-square error (MSE) provided by a preliminary two-way fixed-model 2x2 ANOVA incorporating the housing condition (2 levels) and the drug treatment (2 levels) as between-group factors and time of testing as a blocking factor (8 levels). Estimates of effect sizes were provided by Cohen’s d calculated from ts and degree of freedom. Results. The two groups exhibited significant well-marked cocaine-induced CPP in both 1-day (d = 1.38 and d = 1.11 at ps < .001 one-tailed in exercised and sedentary mice) and 21-day post-conditioning tests (d = 1.09 and d = 1.15 at ps < .001 one-tailed in exercised and sedentary mice). The (small) effects underlying interaction between housing and the drug treatment were not significant for 1-day (d = 0.19 at p = .48 two-tailed; 95% CI -0.35 to 0.73) or 21-day post-conditioning tests (d = 0.05 at p = .87 two-tailed; 95% CI -0.49 to 0.59). Conclusion. If physical exercise in rodents “truly” impacts CPP induced by drugs of abuse under comparable experimental parameters - as suggested by some studies (either positively or negatively) -, our results indicate that the size of such effects may be quite small, an information rarely reported in the literature

Long-term protective effect of wheel-running on cocaine reactivity

Chronic running activity performed during adolescence in C57BL/6J mice induce a protective long term effect on psycho-stimulating effect of cocain

The protective effects of free wheel-running against cocaine psychomotor sensitization persist after exercise cessation in C57BL/6J mice

Previous literature suggests that free access to a running wheel can attenuate the behavioral responsiveness to addictive drugs in rodents. In a few studies, wheel-running cessation accentuated drug responsiveness. Here, we tested whether free wheel-running cessation is followed by (1) an accentuation or (2) an attenuation of cocaine psychomotor sensitization, knowing that no cessation of (continuous) wheel-running is associated with an attenuation of cocaine responsiveness. Male C57BL/6J mice, aged 35 days, were housed singly either with (exercising mice) or without (non-exercising mice) a running wheel. At the end of a period of 36 days, half of the exercising mice were deprived of their wheel whereas the other half of exercising mice kept their wheel until the end of experimentation (which lasted 85 days). The non-exercising mice were housed without wheel throughout experimentation. Testing took place 3 days after exercise cessation. After 2 once-daily drug-free test sessions, mice were tested for initiation of psychomotor sensitization over 13 once-daily injections of 8 mg/kg cocaine. Post-sensitization conditioned activation (saline challenge) and long-term expression of sensitization were assessed 2 or 30 days after the last sensitizing injection (same treatments as for initiation of sensitization), respectively. Exercising mice and mice undergoing wheel-running cessation exhibited comparable degrees of attenuation of all cocaine effects in comparison with the continuously non-exercising mice, which showed the greatest effects. Thus, the efficaciousness of wheel-running at attenuating cocaine sensitization not only resisted to exercise cessation but also was unambiguously persistent (an important effect rarely reported in previous literature)

Evidence for a long-term protection of wheel-running exercise against cocaine psychomotor sensitization in adolescent but not in adult mice

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

No evidence that wheel-running exercise impacts cocaine conditioned place preference in male C57BL/6J mice

peer reviewedWheel-running in rodents can mitigate addiction-related effects of drugs of abuse like cocaine. However, conditioned place preference (CPP) experiments have reported conflicting results, a situation warranting further studies. Our purpose was to test whether wheel-running exercise during adolescence could impact the formation and long-term retention of CPP to cocaine in mice. Male C57BL/6 J mice were individually housed either with (n = 32) or without (n = 32) a running wheel from the age of 35 days. Behavioral testing began 3 weeks after such housing, mice underwent a baseline session followed by 10 once-daily conditioning sessions receiving peritoneal injections of 10 mg/kg cocaine and saline on alternate days (n = 16), control mice receiving saline every day (n = 16). One and 21 days after the last conditioning session, they were tested for CPP. Both groups exhibited comparable well-marked cocaine-induced CPP in both post-conditioning tests resulting in a negligible interaction between housing and the pharmacological treatment (η²p < 0.01). These results, along with the discrepancy found in the literature, question the nature (and the robustness) of the effects that exercise induces on CPP to cocaine. © 201

Long-term effects of exercise during youth or adulthood on cocaine reactivity in mice: qualitative developmental differences

Epidemiological studies suggest that physical exercise could have preventive properties on drugs vulnerability. Animal research showed that rats or mice housed with a running wheel (a model of physical exercise) can exhibit attenuated drug seeking and drug-induced psychomotor hyperactivity in comparison with their sedentary counterparts. Objectives: the aim was to evaluate the longevity of the protective effects of exercise on cocaine vulnerability and the influence of the developmental stage during which exercise is applied (in 4 experiments). Method: females and males C57BL/6J mice, aged 28 (youth) or 77 days (adults) were housed with (n=56) or without (n=28) a running wheel. After 3 weeks, half of the exercised mice (n=28) were deprived of their wheel (3 housing conditions/experiment). Three weeks later, mice were tested for sensitization to the psychomotor-activating effects of 8 mg/kg cocaine over 9 once-daily sessions (controls: saline solution). Mice were also tested 30 days later for their long-term expression of sensitization. Results: continuous wheel-running housing reduced cocaine responsiveness in both females and males regardless of the age on which exercise was introduced. Exercise performed exclusively in youth, but not over adulthood, reduced durably cocaine responsiveness, particularly in females. Conclusion: the likelihood of the long-term protection of exercise against cocaine responsiveness may depend on the age of exercise application and the gender

Wheel-running exercise before and during gestation against acute and sensitized cocaine psychomotor-activation in offspring.

peer reviewedWhile 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/6 J 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=0.02), whereas there was no evidence for such a difference in males (d=0.34, p=0.17). 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 −0.13 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