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1.

Introduction

Chronic cocaine use is associated with some executive deficits. We assessed executive functions using ecologically valid tests in chronic cocaine users.

Objectives

To investigate the relationship between executive deficits and three measures of severity of cocaine use: years of use, quantity used, and frequency of use.

Methods

Twenty-four cocaine users were compared with twenty-seven community controls. We used Student's t-test and Chi-squared to compare means and categorical variables, respectively. Linear regression analyses for the adjusted comparative analysis between cases and controls, and severity of cocaine use among cocaine users were performed.

Results

Chronic cocaine users performed worse on measures of attention and working memory (Forward and Backward Digit Span, p < .001), set-shifting abilities (difference score between the Trail Making B and A, TMB-A, p = .006), cognitive test of mental flexibility and response inhibition (Rule Shift Cards) (p < .001), and prefrontal functioning (Wisconsin Card Sorting Test, WCST, p = .023) than controls. Years of cocaine use were associated with deficits in the Backward Digit Span (p = .041; CI 95%: −.760 to −.002), the TMB-A (p = .026; CI 95%: .687 to 9.761), the Zoo Map (p = .034; CI 95%: −.480 to −.021), and the Rule Shift Cards (p = .006; CI 95%: −.836 to −.164), among others. Quantity of cocaine use was associated with executive deficits measured by the Forward Digit Span (p = .007; CI 95%: −.727 to −.133), the TMB-A (p = .021; CI 95%: 5.304-57.945), and the number of perseverative errors in the WSCT (p = .002; CI 95%: −10.654 to −2.800). Frequency of cocaine was associated with deficits in the Backward Digit Span (p = .042; CI 95%: −1.548 to −.030).

Conclusions

Chronic use of cocaine is associated with executive deficits, which may influence patients’ functionality, prognosis, and therapeutic failure.  相似文献   

2.

Background

Binge drinking may lead to brain damage. The aim of the present study was to compare the cognitive abilities of binge and non-binge drinkers in tasks which test functions linked to discrete areas of the prefrontal cortex.

Methods

Non-binge and binge drinkers were identified according to their binge score derived from the Alcohol Use Questionnaire. Cognitive performance was tested with the Spatial Working Memory task (SWM) linked to the dorsolateral prefrontal cortex, Intra/Extradimensional Shift and reversal task (IED) linked to dorsolateral prefrontal cortex (shift) and to orbitofrontal cortex (reversal), Paired Associates Learning task (PAL) linked to temporal cortex, and Reaction Time Task (RTI) a task measuring motor impulsivity (Inferior frontal gyrus). Personality traits, alcohol outcome expectancies and mood were also evaluated.

Results

Binge drinkers recorded a significantly shorter movement time to target in the RTI, and completed fewer stages on first trial in the PAL, compared with non-bingers. In the IED as well as in the SWM, only female binge drinkers were more impaired than non-binge drinkers.

Conclusions

Functions linked to dorsolateral prefrontal cortex may be more impaired in female, whereas functions linked with the temporal lobe may be impaired in both male and female binge drinkers compared to non-binge drinkers. Functions linked to orbitofrontal cortex were not impaired. The increased speed of response in the RTI in binge drinkers may indicate an increased motor impulsivity in binge drinkers.  相似文献   

3.

Background

Adolescence is a time of considerable neurodevelopment. Binge drinking (BD) during this period increases the vulnerability to its neurotoxic effects. This longitudinal study aimed to investigate the relationship between BD trajectory over university years and neuropsychological functioning.

Methods

Cohort-study. Two-year follow-up. A total of 89 university students were assessed: 40 Non-BD (at Initial and Follow-up), 16 Ex-BD (BD at Initial but not at Follow-up) and 33 BD (at both times). Neuropsychological assessment of working memory, episodic memory and executive abilities was carried out during their first (Initial) and third (Follow-up) academic year at the University of Santiago de Compostela.

Results

BD subjects performed less well on the Wechsler Memory Scale-III (WMS-III) Logical Memory Subtest (immediate theme recall, P = .034; delayed theme recall, P = .037; and percent retention, P = .035) and committed more perseverative errors on the Self-Ordered Pointing Task (SOPT) (P = .021) than Non-BD. There were no differences between Ex-BD and Non-BD.

Conclusions

Binge drinking trajectory during adolescence is associated with neuropsychological performance. Persistent BD, but not Ex-BD, is associated with verbal memory and monitoring difficulties. This is compatible with the hypothesis that heavy alcohol use during adolescence may affect cognitive functions that rely on the temporomesial and dorsolateral prefrontal cortex.  相似文献   

4.

Rationale

Methamphetamine abuse and dependence are significant public-health concerns. Behavioral therapies are effective for reducing methamphetamine use. However, many patients enrolled in behavioral therapies are unable to achieve significant periods of abstinence suggesting other strategies like pharmacotherapy are needed.

Objectives

This experiment determined the physiological and subjective effects of acutely administered intranasal methamphetamine during atomoxetine maintenance in seven non-treatment seeking stimulant-dependent participants. Atomoxetine was chosen for study because it blocks reuptake at the norepinephrine transporter and increases extracellular dopamine levels in the prefrontal cortex. In this way, atomoxetine might function as an agonist replacement therapy for stimulant-dependent patients.

Methods

After at least 7 days of maintenance on atomoxetine (0 and 80 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 min.

Results

Intranasal methamphetamine produced prototypical physiological and subjective effects (e.g., increased heart rate, blood pressure, temperature and subjective ratings of Good Effects). Atomoxetine maintenance augmented the heart rate-increasing effects of methamphetamine, but attenuated the pressor effects. The subjective effects of intranasal methamphetamine were similar during atomoxetine and placebo maintenance.

Conclusions

These results suggest that methamphetamine can be safely administered to participants maintained on atomoxetine, but whether it might be an effective pharmacotherapy for methamphetamine dependence remains to be determined.  相似文献   

5.

Background

In addition to cognitive and emotional processing dysfunction, chronic cocaine users are also impaired at simple sensorimotor tasks. Many diseases characterized by compulsive movements, repetitive actions, impaired attention and planning are associated with dysfunction in frontal-striatal circuits. The aim of this study was to determine whether cocaine users had impaired frontal-striatal connectivity during a simple movement task and whether this was associated with sensorimotor impairment.

Methods

Functional MRI data were collected from 14 non-treatment seeking cocaine users and 15 healthy controls as they performed a finger-tapping task. Functional coupling was quantified by correlating the timecourses of each pair of anatomically connected regions of interest. Behavioral performance was correlated with all functional coupling coefficients.

Results

In controls there was a significant relationship between the primary motor cortex and the supplementary motor area (SMA), as well as the SMA and the dorsal striatum during ongoing movement. Cocaine users exhibited weaker fronto-striatal coupling than controls, while the cortical-cortical coupling was intact. Coupling strength between the SMA and the caudate was negatively correlated with reaction time in the users.

Conclusions

The observation that cocaine users have impaired cortical-striatal connectivity during simple motor performance, suggests that these individuals may have a fundamental deficit in information processing that influences more complex cognitive processes.  相似文献   

6.

Objective(s)

To estimate the incidence rate of initiation into drug injection and to identify predictors of initiation into drug injection separately among street girls and boys.

Design

Data from two consecutive prospective street youth cohort studies (1995-2001 and 2001-2005) were used to conduct these analyses, stratified by gender.

Methods

Data were collected using semi-annual interviewer-administered questionnaires. Variables from the following domains were considered in Cox regression models: socio-demographic characteristics, early and current substance abuse, marginalization, childhood traumatic sexual events and injection exposure.

Results

Of the 946 youth who had never injected drugs at study entry, 86.4% completed at least two questionnaires representing 243 girls and 574 boys. Incidence rates of injection of 7.0 and 5.9 per 100 person-years were observed among these girls and boys respectively. Among girls, cocaine or crack use (adjusted hazard ratio (AHR) = 1.97), heroin use (AHR = 2.86), homelessness (AHR = 2.49) and hanging out regularly with people who inject (AHR = 4.46) all independently increased risk of first injection. Among boys, age decreased risk of initiating injection (AHR = 0.90/year), while cocaine or crack use (AHR = 2.14), heroin use (AHR = 3.56), homelessness before age 16 (AHR = 1.68), incest or rape before age 14 (AHR = 1.98) and hanging out regularly with people who inject (AHR = 1.66) all independently increased this risk.

Conclusions

Our findings suggest similar rates of initiation among girls and boys; however, factors associated with initiation vary by gender. This might lead to the design of more effective programs to prevent initiation into drug injection.  相似文献   

7.

Objective

The etiology of diabetes associated cognitive decline is multifactorial and involves insulin receptor down regulation, neuronal apoptosis and glutamatergic neurotransmission. The study was designed to evaluate the impact of tocotrienol on cognitive function and neuroinflammatory cascade in streptozotocin-induced diabetes.

Research design and method

Streptozotocin-induced diabetic rats were treated with tocotrienol for 10 weeks. Morris water maze was used for behavioral assessment of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus were prepared for the quantification of acetylcholinesterase activity, oxidative-nitrosative stress, tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), NFκβ and caspase-3.

Results

After 10 weeks of streptozotocin injection, the rats produced significant increase in transfer latency which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, TNF-α, IL-1β, caspase-3 activity and active p65 subunit of NFκβ in different regions of diabetic rat brain. Interestingly, co-administration of tocotrienol significantly and dose-dependently prevented behavioral, biochemical and molecular changes associated with diabetes. Moreover, diabetic rats treated with insulin-tocotrienol combination produced more pronounced effect on molecular parameters as compared to their per se groups.

Conclusions

Collectively, the data reveal that activation of NFκβ signaling pathway is associated with diabetes induced cognitive impairment and point towards the therapeutic potential of tocotrienol in diabetic encephalopathy.  相似文献   

8.

Rationale

Quetiapine has been shown to be a promising medication for the treatment of alcoholism. As an atypical antipsychotic medication with antagonist activity at D1 and D2, 5-HT1A and 5-HT2A, H1 and α1 and α2 receptors, quetiapine has been found to decrease impulsivity in other psychiatric disorders but its effects on impulsivity have not been studied in alcohol dependent patients.

Objective

This study seeks to test the effects of quetiapine on a specific dimension of impulsivity, namely response inhibition. This pilot study seeks to further elucidate the mechanisms of action of quetiapine for alcohol use disorders.

Method

A total of 20 non-treatment seeking alcohol dependent individuals were randomized to one of the following conditions in a double-blind, placebo-controlled design: (1) quetiapine (400 mg/day); or (2) matched placebo. Participants completed two counterbalanced intravenous placebo-alcohol administration sessions as well as behavioral measure of response inhibition (i.e. stop signal task) pre and post placebo-alcohol administration sessions.

Results

Analyses revealed a significant effect of quetiapine in improving response inhibition as measured by the stop signal task. These results provide preliminary evidence suggesting that quetiapine improves response inhibition in alcohol dependent patients, as compared to placebo.

Conclusion

This pilot study contributes a novel putative mechanism of action of quetiapine in alcoholism, namely an improvement in response inhibition.  相似文献   

9.

Background

P-glycoprotein (P-gp), an efflux transporter localized in the blood-brain barrier, limits the access of multiple xenobiotics to the central nervous system (CNS). For the new antipsychotic aripiprazole and its active metabolite dehydroaripiprazole differences in disposition in blood and brain were investigated after acute and sub-chronic administration in a P-gp knockout mouse model.

Methods

Serum and brain concentrations of both drugs were measured at several time points 1-24 h after i.p. injection of 10 mg/kg aripiprazole and after 11 days of sub-chronic administration in several tissues. Moreover, the expression of P-gp was determined by Western blot analysis after sub-chronic administration of the drug.

Results

In both wild type and abcb1ab (−/−) mice concentration of aripiprazole in brain were up to 9 fold higher than in serum. For dehydroaripiprazole the mean brain to serum ratios were below two. Brain to serum concentrations of both substances were significantly higher after acute and sub-chronic administration in connection to the expression of P-gp indicated by higher levels in abcb1ab (−/−) mice especially for dehydroaripiprazole.Sub-chronic aripiprazole treatment in WT animals had no effect on P-gp expression in the blood-brain barrier.

Conclusions

Aripiprazole and, even more pronounced its active metabolite dehydroaripiprazole could be identified as substrates of P-gp. The efflux transporter P-gp must therefore be considered as a relevant factor that contributes to wanted or unwanted clinical effects in patients treated with aripiprazole.  相似文献   

10.

Background

Casiopeína IIgly (Cas IIgly) [Cu(4,7-dimethyl-1,10-phenanthroline)(glycinate)]NO3 induce oxidative damage in different human tumour cell strains, as the known anticancer agent cisplatin (CDDP) does.

Purpose

To compare glutathione (GSH) depletion induced by Cas IIgly and CDDP in murine melanoma B16 cells and its relationship with their antiproliferative effect.

Materials and methods

Cell growth was determined according to the sulforhodamine B assay. Intracellular GSH levels were measured by the reduction of Ellman’s reagent (DTNB).

Results

Cas IIgly IC50 in B16 cells was 54.5 μM (24.21 μg/mL), which depleted GSH from 1092 to 585 ng per million cells in a 30 min incubation period. In the other hand, CDDP was less toxic at the same conditions with an IC50 equal to 197.76 μM (59.33 μg/mL), and depleted GSH to 50% of the normal only after a longer exposure period (4 h). The addition of 1.8 mM ascorbic acid (Asc) or 1 mM buthionine sulfoximine (BSO) enhanced Cas IIgly toxicity, whereas it was prevented by 100 U/mL catalase. BSO sensitised B16 cells to CDDP, but neither Asc or catalase modified CDDP effects.

Conclusions

The antiproliferative effect of both drugs correlated to intracellular GSH levels. Unlike CDDP, GSH depletion induced by Cas IIgly occurs earlier, it is enhanced by ascorbic acid and preventable by catalase. Redox cycles, feasible only with Cas IIgly, may be an important difference in their mode of action.  相似文献   

11.

Background

Cocaine dependence is associated with cognitive deficits and altered task-related cerebral activation in cognitive performance (see Li and Sinha, 2008, for a review). Relatively little is known whether these individuals are also impaired in regional brain activation of the default mode network (DMN). We demonstrated previously that greater activation of the default brain regions precedes errors in a stop signal task performed by healthy controls (SST, Li et al., 2007). We seek to determine whether individuals with cocaine dependence are impaired in DMN activity, specifically activity preceding error, as compared to the healthy people. We also examine the relation to years of cocaine use.

Methods

Individuals with cocaine dependence (CD, n = 23) and demographics-matched healthy controls (HC, n = 27) performed a SST that employed a tracking procedure to adjust the difficulty of stop trials and elicit errors approximately half of the time. Blood oxygenation level dependent (BOLD) signals of go trials preceding stop error as compared to those preceding stop success trials were extracted with generalized linear models using statistical parametric mapping.

Results

HC showed activation of bilateral precuneus and posterior cingulate cortices and ventromedial prefrontal cortex (vmPFC) preceding errors during the SST. In contrast, despite indistinguishable stop signal performance, CD did not show these error predicting activations. Furthermore, the effect size of error-preceding vmPFC activation was inversely correlated with years of cocaine use.

Conclusions

These findings indicate DMN deficits and could potentially add to our understanding of the effects of chronic cocaine use on cerebral functions in cocaine dependence. Work to further clarify potential changes in functional connectivity and gray matter volume is warranted to understand the relevance of DMN to the pathology of cocaine misuse.  相似文献   

12.

Purpose

Although most children with acute lymphoblastic leukemia (ALL) are cured, a subset manifests persistent, focal cognitive deficits. Methotrexate (MTX), a key component of leukemia treatment, is suspected to contribute to treatment-induced cognitive dysfunction. We sought to establish a rodent model in order to further investigate the underlying pathophysiology.

Procedures

Intraperitoneal MTX was given to Long-Evans rats on two schedules: acute (250 mg/kg once during adulthood), or chronic (1 mg/kg twice weekly ×4 doses, beginning at postnatal day 15, then weekly ×6). Control rats were given saline injections on the same schedules. All male rats subsequently underwent behavioral testing designed to assess cognitive domains frequently impaired among children treated for ALL. Cerebrospinal fluid and serum folate concentrations were measured by HPLC.

Findings

Both acute and chronic MTX administration produced spatial memory deficits, without significantly altering visual memory, general exploration, activity or motor coordination. MTX administration was also associated with a marked reduction in serum and CSF folate and a decrease in the ratio of CSF S-adenosylmethionine to S-adenosylhomocysteine.

Conclusions

Similar to children treated for ALL, rats given systemic MTX develop focal cognitive deficits along with expected alterations in folate physiology.  相似文献   

13.

Background

This study sought to collect information on the former legal-high ‘mephedrone’ using a web-based survey targeted at mephedrone users.

Methods

The survey was advertised on websites frequented by drug users. Individuals were invited to complete the survey if they had taken mephedrone on at least one occasion in the past.

Results

One thousand and six completed forms were received from declared users, making this the largest survey on mephedrone to date.

Conclusion

Results showed that mephedrone users consider its effects to compare best with those of MDMA, and while MDMA was considered marginally safer and its effects more pleasurable, mephedrone's appeal lay in its availability, low price and reliable purity.  相似文献   

14.

Background

Alcohol use disorders (AUDs) are highly prevalent and associated with non-adherence to antiretroviral therapy, decreased health care utilization and poor HIV treatment outcomes among HIV-infected individuals.

Objectives

To systematically review studies assessing the impact of AUDs on: (1) medication adherence, (2) health care utilization and (3) biological treatment outcomes among people living with HIV/AIDS (PLWHA).

Data sources

Six electronic databases and Google Scholar were queried for articles published in English, French and Spanish from 1988 to 2010. Selected references from primary articles were also examined.

Review methods

Selection criteria included: (1) AUD and adherence (N = 20); (2) AUD and health services utilization (N = 11); or (3) AUD with CD4 count or HIV-1 RNA treatment outcomes (N = 10). Reviews, animal studies, non-peer reviewed documents and ongoing studies with unpublished data were excluded. Studies that did not differentiate HIV+ from HIV− status and those that did not distinguish between drug and alcohol use were also excluded. Data were extracted, appraised and summarized.

Data synthesis and conclusions

Our findings consistently support an association between AUDs and decreased adherence to antiretroviral therapy and poor HIV treatment outcomes among HIV-infected individuals. Their effect on health care utilization, however, was variable.  相似文献   

15.

Background

This paper investigates how stress interacts with alcohol consumption in subjects with a family history of alcoholism. One mechanism for increases in alcohol intake may be that stress alters the subjective effects produced by the drug.

Methods

58 healthy volunteers, divided into two groups of family history positive (FHP) and two groups of family history negative (FHN) participated in two laboratory sessions, in which they performed in one out of two sessions a stress task. Then subjects were allowed to choose up to six additional drinks of ethanol or placebo depending on which session they were randomly assigned to start with.

Results

It was found that FHP subjects increased their consumption of alcohol after stress.

Conclusions

It is possible that both stress and alcohol specifically exaggerate the feelings of the reward in the FHP individuals in such way that it may increase the likelihood of consuming more alcohol.  相似文献   

16.

Background

Research on harm reduction has typically focused on broad-based or organisational strategies such as needle exchange and opiate substitute programmes. Less attention has been paid to the self-directed harm reduction practices of substance users themselves. Few studies have focused on sexual minority populations such as gay and bisexual men and fewer still on the marginalised groups that constitute these populations. This paper identifies self-directed harm reduction strategies among substance using ethno-racially diverse gay and bisexual men.

Methods

This article presents findings from the Party Drugs Study in Toronto's gay dance club scene, a community-based qualitative study in Toronto, Canada. We present a thematic analysis of interviews with 43 gay and bisexual men from diverse ethno-racial backgrounds about their substance use in the gay dance club scene.

Findings

We identify five self-directed harm reduction strategies: rationing, controlling or avoiding mixing, controlling quality, maintaining a healthy lifestyle, and following guidelines during substance use.

Conclusions

We discuss our findings in relation to prior research and to critical theory. We suggest that drug users’ awareness of possible harm, and their personal investment in harm reduction, constitute a viable platform from which community-based and public health organisations may promote and strengthen harm reduction among gay and bisexual men from ethno-racially diverse backgrounds.  相似文献   

17.

Objectives

Curcumin, a major active component of Curcuma longa, possesses antidepressant effects that are mediated by the 5-HT system. However, little is known about the effect of curcumin on the behavioral consequences of methamphetamine (METH).

Methods

The subjects were male, adult Sprague-Dawley rats. In Experiment 1, the effects of 20 and 40 mg/kg curcumin (i.p.) on response rates and breakpoints of 0.06 mg/kg/infusion METH were evaluated. In Experiment 2, rats were self-administering METH for 10 days followed by a 14-day abstinence period. During the abstinence period, the animals were treated with DMSO, 20 or 40 mg/kg curcumin. All rats were then tested for extinction responding and cue-induced reinstatement. In Experiment 3, rats were treated with DMSO, 20, or 40 mg/kg curcumin15 min before a METH-induced locomotor activity test for 14 consecutive days. In Experiment 4, rats were pretreated with DMSO or curcumin (20 mg/kg or 40 mg/kg) for 13 days and were subsequently tested for METH-induced locomotor activity on the 14th day. In Experiment 5, three groups were tested for locomotor activity after an injection of DMSO, 20, or 40 mg/kg curcumin. The test was repeated for 14 days.

Results

Curcumin produced little effect on response rates and breakpoints maintained by METH. Chronic treatment of only 40 mg/kg curcumin during the abstinence phase enhanced cue-induced reinstatement of METH self-administration. Chronic administration of curcumin increased METH-induced sensitization of locomotor activity at the lower (20 mg/kg) but not higher (40 mg/kg) dose. However pretreatment of curcumin alone showed no significant effect on acute locomotor responses to METH and locomotor responses per se.

Conclusions

Curcumin enhanced, rather than inhibited the behavioral effects of METH.  相似文献   

18.

Background

To evaluate the predictive validity of early response compared to other well-known predictor variables in acutely ill first-episode patients.

Methods

112 patients were treated with a mean dosage of 4.14 mg (± 1.70) haloperidol and 112 patients with a mean dosage of 4.17 mg (± 1.55) risperidone for a mean inpatient treatment duration of 42.92 days (± 16.85) within a double-blind, randomized controlled trial. Early response was defined as a ≥ 30% improvement in the PANSS total score by week 2, response as a ≥ 50% reduction in the PANSS total score from admission to discharge and remission according to the consensus criteria. Univariate tests and logistic regression models were applied to identify significant predictors of response and remission.

Results

52% of the patients were responders and 59% remitters at discharge. Non-remitters at discharge were hindered from becoming remitters mainly by the presence of negative symptoms. Univariate tests revealed several significant differences between responders/non-responders and remitters/non-remitters such as age, severity of baseline psychopathology as well as the frequency of early response. Both early response (p < 0.0001) and a higher PANSS positive subscore at admission (p = 0.0002) were identified as significant predictors of response at discharge, whereas a shorter duration of untreated psychosis (p = 0.0167), a lower PANSS general psychopathology subscore (p < 0.0001), and early treatment response (p = 0.0002) were identified as significant predictors of remission.

Conclusion

Together with the finding that early response is a significant predictor of response and remission, the relevance and predictive validity of negative and depressive symptoms for outcome is also highlighted.  相似文献   

19.

Background

Myanmar has long been a focus of the international community as a major opium poppy cultivation region.

Method

This study used remote sensing technology and ground verification to monitor opium poppy cultivation for three opium poppy growth seasons in North Myanmar.

Results

The study found that opium poppy cultivation has remained high. In 2005-6, 2006-7 and 2007-8 growing seasons the total areas monitored were 52,482 km2, 178,274 km2 and 236,342 km2 and the total cultivated area of opium poppy was 8959 ha, 18,606 ha and 22,300, respectively. This was significantly less than cultivation levels reported during the 1990s. The major cultivation regions were located in Shan State, producing 88% of total poppy cultivation in North Myanmar in 2007-8. The opium poppy was mainly cultivated in the interlocking regions controlled by the local armed forces in Shan State. The field survey noted that most households in this area were poor and poppy cultivation was a main source of income. There were also differences between our figures on poppy cultivation and those reported by United Nations Office on Drugs and Crime.

Conclusion

Our study shows that although the opium poppy cultivation in North Myanmar has reduced over recent years, it remains a major producer of opium and to which the international community needs to pay attention, especially in those areas controlled by local armed forces.  相似文献   

20.

Rationale

Early-life stressful experiences are associated to alterations in behavioural responses and development of psychiatric and neurodegenerative diseases. In rodents, individual housing is considered as a stressful condition whilst enriched environment can protect against stress and its negative consequences. Neuroendocrine responses to stress can also be altered by early-life experiences and seem to contribute to behavioural alterations induced by changes in housing conditions.

Objective

To develop an improved procedure of social isolation throughout development (from pre-adolescence to adulthood) in CD1 mice and to elucidate its effects on behavioural parameters related to stress and neuroendocrine responses compared to enriched or social conditions.

Materials and methods

CD1 male mice (PND 21) were housed in social/standard conditions, enriched conditions or isolated conditions during seven weeks. After that, different relevant behaviours were evaluated, including locomotor activity, anxiety-like and despair behaviour. Levels of plasma corticosterone were also analysed before and after a stressful event.

Results

CD1 mice exposed to an isolated environment exhibited higher locomotion and anxiety-like responses than animals exposed to social or enriched conditions. In addition, isolated animals showed lower basal plasma corticosterone than social or enriched ones but after a stressful event the elevation of plasma corticosterone was higher, suggesting an enhanced response of the HPA axis to a novel and stressful situation.

Conclusions

Social interaction is an important feature to display an appropriate behavioural and neuronal development. Habituation to novel stimuli is impaired in subjects exposed to social isolation and induces increased excitability response to stressful events. Social deprivation increases the possibility of altered neuronal function and could facilitate the development of neuropsychiatric disorders in adulthood.  相似文献   

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