Amphetamine-type stimulant use and HIV/STI risk behaviour among young female sex workers in Phnom Penh, Cambodia

Background

Use of amphetamine-type substances (ATS) has been linked to increased risk of HIV and other sexually transmitted infections (STI) worldwide. In Cambodia, recent ATS use is independently associated with incident STI infection among young female sex workers (FSWs).

Methods

We conducted 33 in-depth interviews with women (15-29 years old) engaged in sex work to explore ATS use and vulnerability to HIV/STI.

Results

Participants reported that ATS, primarily methamphetamine in pill and crystalline forms (yama), were cheap, widely available and commonly used. Yama was described as a “power drug” (thnam kamlang) which enabled women to work long hours and serve more customers. Use of ATS by clients was also common, with some providing drugs for women and/or encouraging their use, often resulting in prolonged sexual activity. Requests for unprotected sex were also more common among alternatives intoxicated clients and strategies typically employed to negotiate condom use were less effective.

Conclusion

ATS use was highly functional for young women engaged in sex work, facilitating a sense of power and agency and highlighting the occupational significance and normalization of ATS in this setting. This highly gendered dynamic supports the limited but emerging literature on women's use of ATS, which to date has been heavily focused on men. Results indicate an urgent need to increase awareness of the risks associated with ATS use, to provide women with sustainable alternatives for income generation, to better regulate the conditions of sex work, and to work with FSWs and their clients to develop and promote culturally appropriate harm reduction interventions.     

Malnutrition in a population of HIV-positive and HIV-negative drug users living in Chennai, South India

Background

Malnutrition is a strong predictor of poor outcomes in people living with HIV (PLHIV). Drug users are at increased risk of malnutrition regardless of whether or not they are infected with HIV. Little data exists on the nutritional status of drug users (with or without HIV infection) in India.

Methods

We describe and compare the nutrition and metabolic status of 107 HIV-positive and 193 HIV-negative male clients of a community-based drop-in center for injection drug users in Chennai, India. Measures of nutrition and metabolic status include body composition, dietary intake, food insecurity, and serum lipid levels.

Results

We found poor overall nutritional status in both the HIV-positive and HIV-negative clients, with HIV-positive men faring worse on some parameters. Both groups had extremely low percent body fat, but levels in HIV-positive participants were significantly lower (6.5% versus 7.9%, p = .01). HIV-positive men also had significantly lower total caloric and fat intakes compared to HIV-negative men. A considerable proportion (70%) of both HIV-positive and HIV-negative drug users were food insecure. HDL cholesterol levels were significantly lower and below normal range in the HIV-positive compared to HIV-negative men.

Conclusions

The high levels of food insecurity and poor nutritional status in this population, regardless of HIV status, indicates critical need for intervention. Improving nutritional status in those who are infected with HIV prior to initiation of antiretroviral treatment may help patients to reap the full benefits of therapy.     

A venue analysis of predictors of alcohol use prior to sexual intercourse among female sex workers in Senggigi, Indonesia

Background

Female sex workers’ (FSWs’) use of alcohol, a known disinhibitor to risk behaviour, has been largely understudied. Knowledge of how various sex work venues influence FSW's alcohol consumption before engaging in commercial sex is even rarer. Our analysis identifies those factors across three types of sex-work venues that predict alcohol use among FSWs prior to paid sexual intercourse with clients. Our data were collected through structured interviews with FSWs engaging in commercial sex in Senggigi Beach, Lombok Island in the eastern Indonesian province of West Nusa Tenggara.

Methods

Employing a cross-sectional and multilevel design, three categories of venues where FSWs meet clients in Senggigi were sampled: (1) discotheques and bars (freelance), (2) brothels, and (3) recreational enterprises such as karaoke establishments and massage parlors. The sample consisted of 115 women “nested” within 16 sex work venues. The FSWs reported on 326 clients interactions.

Results

Results show that FSWs consumed alcohol before commercial sex with 157 (48%) of the 326 clients interactions. Alcohol use varied by differences in HIV policies and services offered at the sex work venue, the FSW's educational level and age, and client characteristics.

Conclusion

Alcohol use is common prior to sexual intercourse among FSWs and their clients in Senggigi, and the venue where FSWs meet their clients influences the women's alcohol use. Freelancers were likelier to use alcohol than those who work at brothels and recreational enterprises. Given the recognized links between alcohol use prior to sex and high risk behaviour, HIV prevention programmes that discourage alcohol use should be introduced to both women who engage in commercial sex and also sex-work venue managers, owners, and clients.     

Fear-potentiated startle, but not light-enhanced startle, is enhanced by anxiogenic drugs

Rationale and objectives

The light-enhanced startle paradigm (LES) is suggested to model anxiety, because of the non-specific cue and the long-term effect. In contrast, the fear-potentiated startle (FPS) is suggested to model conditioned fear. However, the pharmacological profiles of these two paradigms are very similar. The present study investigated the effects of putative anxiogenic drugs on LES and FPS and aimed at determining the sensitivity of LES for anxiogenic drugs and to potentially showing a pharmacological differentiation between these two paradigms.

Methods

Male Wistar rats received each dose of the α₂-adrenoceptor antagonist yohimbine (0.25-1.0 mg/kg), the 5-HT_2C receptor agonist m-chlorophenylpiperazine (mCPP, 0.5-2.0 mg/kg) or the GABA_A inverse receptor agonist pentylenetetrazole (PTZ, 3-30 mg/kg) and were subsequently tested in either LES or FPS.

Results

None of the drugs enhanced LES, whereas mCPP increased percentage FPS and yohimbine increased absolute FPS values. Furthermore, yohimbine increased baseline startle amplitude in the LES, while mCPP suppressed baseline startle in both the LES and FPS and PTZ suppressed baseline startle in the FPS.

Conclusions

In contrast to findings in the FPS paradigm, none of the drugs were able to exacerbate the LES response. Thus, a clear pharmacological differentiation was found between LES and FPS.     

Concurrent heroin use among methadone maintenance clients in China

Background

The study examined concurrent illicit heroin use among methadone maintenance clients in China and its association with clients' demographic characteristics, treatment experience, and personal social network.

Methods

Face-to-face surveys were conducted with 178 clients randomly recruited from six methadone maintenance treatment (MMT) clinics in Sichuan, China. Concurrent heroin use was measured based on self-report of heroin use during the past 30 days and a confirmatory urine morphine test. The participants' demographic characteristics and treatment factors were measured and examined. The drug use status of their family members and friends was also assessed.

Results

A total of 80 participants (44.9%) who either reported illicit heroin use in the past 30 days or had a positive urine test were defined as using heroin concurrently. Having drug-using friends was significantly associated with increased concurrent heroin use. Longer length of treatment (2 years or longer) was associated with increased concurrent heroin use. Among those who had both drug-using family members and friends, more women (71.4%) than men (50.0%) used heroin. For those who had no drug-using family members or friends, more men (34.8%) than women (20.8%) used heroin.

Discussion

Study findings indicate an urgent need to address concurrent illicit heroin use among MMT clients. Further examination of the influence of social networks on concurrent drug abuse behavior is encouraged. Results also highlight the importance of understanding gender differences in treatment seeking and behavioral changes, which is crucial to the development of gender-specific treatment strategies.     

The prevalence and correlates of buprenorphine inhalation amongst opioid substitution treatment (OST) clients in Australia

Background

Diversion and injection of buprenorphine (Subutex^®) and buprenorphine-naloxone (Suboxone^®) have been well documented. Recent international research and local anecdotal evidence suggest that these medications are also used by other routes of administration, including smoking and snorting.

Methods

A cross-sectional sample of 440 opioid substitution treatment (OST) clients was recruited through pharmacies and clinics in three Australian jurisdictions, and interviewed face-to-face using a structured questionnaire. Eligible participants were those aged 18 or over, who had resided in their home state for at least six months, and had been in their current treatment episode for at least 4 weeks. We compared differences in characteristics between clients who had ever inhaled (smoked or snorted) buprenorphine (including buprenorphine-naloxone) and other OST clients. Logistic regression was used to identify correlates of buprenorphine inhalation. Sixty-eight clients who had never used buprenorphine were excluded from analysis.

Results

Sixty-five clients (18%) reported having ever inhaled buprenorphine, with Subutex^® smoking being most common, reported by 50 clients (77%). In multivariable logistic regression, those who reported ever inhaling buprenorphine were significantly more likely to: be aged 35 or younger, have ever been in prison and have ever injected buprenorphine. Clients from New South Wales and Victoria were significantly less likely to have ever inhaled buprenorphine than those from South Australia.

Conclusions

Our data indicates that the inhalation of buprenorphine has occurred in a significant minority of Australian OST clients. The motivations, contexts and potential health consequences of buprenorphine use by these atypical routes of administration, particularly in a correctional setting, warrant further exploration.     

A procedure that differentiates unintentional from intentional overdose in opioid abusers

Objective

The purpose of this study is to develop a procedure for assessing unintentional overdose (OD) in opiate abusers that differentiates it from intentional OD, and provides reliable information about the incident.

Methods

A sample of 121 patients in a methadone maintenance program at an urban university hospital completed a baseline assessment. A total of 70 participants completed an identical assessment at least 14 days later. The ability of an OD item to differentiate unintentional OD from intentional OD was tested, as was the test-retest reliability of questions assessing symptoms and treatment of OD.

Results

The procedure is reliable and differentiated unintentional OD from intentional OD. Questions assessing symptoms of OD were endorsed in almost every unintentional OD incident, although reliability was affected by loss of consciousness. The reliability of questions assessing emergency treatment and Narcan administration was outstanding.

Conclusions

Our procedure for assessing OD differentiates unintentional OD from intentional OD. The use of follow-up questions assessing acute treatment for OD is recommended. Items concerning symptoms of OD are not needed to confirm the presence of an OD, but may be used to clarify whether an event was an OD.     

A qualitative study exploring the reason for low dosage of methadone prescribed in the MMT clinics in China

Objectives

Dosage of methadone maintenance therapy (MMT) is an important factor influencing retention in methadone treatment. MMT clients in China received lower dosages of methadone compared with those provided in other countries. The objective of this study is to elucidate the reason for the low methadone dosage prescribed in MMT clinics in China.

Methods

Twenty-eight service providers were recruited from the MMT clinics in Zhejiang and Jiangxi Provinces, China. Qualitative in-depth interviews were conducted to ascertain the procedure for prescribing methadone in the MMT clinics.

Results

The average dosage prescribed in the 28 clinics was 35 mg/person/day. Four major themes resulting in low dosage of methadone were identified: (1) the service providers fear the liability resulting from large doses of methadone in combination with other substances which might result in overdose fatalities, (2) lack of understanding of harm reduction which resulted in low acceptance of the long term maintenance treatment approach, (3) break-down in communication between clients and service providers about dosage adjustment, and (4) dosage reduction is perceived by most service providers as an effective way to treat the side-effects associated with MMT.

Conclusions

The findings of the study highlighted the necessity to formulate clear guidelines concerning individualized dosage management and to improve training among service providers’ in MMT clinics in China.     

Adolescent nicotine exposure sensitizes cue-induced reinstatement of cocaine seeking in rats bred for high and low saccharin intake

Background

Quit attempts may have different outcomes based on menstrual cycle phase on quit day. This is the first preliminary study examining whether smoking cessation outcomes vary by menstrual cycle phase of quit date in women receiving a 6-week open trial of sustained release (SR) bupropion.

Methods

Thirty-three treatment-seeking premenopausal women were studied. Abstinence outcomes were compared for women quitting during the luteal versus follicular phase.

Results

Women receiving bupropion SR whose self-selected quit date occurred in the luteal phase had significantly higher rates of point prevalence abstinence during the final week of a 6-week post-quit treatment period than women quitting in the follicular phase (62.5% versus 29.4%; p < 0.05). A similar, but non-significant, pattern of findings was demonstrated for continuous abstinence during the treatment phase and for point prevalence abstinence at 3-month follow-up.

Conclusions

Women receiving bupropion SR were significantly more likely to be abstinent at treatment completion if quitting occurred during the luteal phase. This is consistent with recent findings of outcome related to cycle phase at quit date in the absence of pharmacotherapy, and differs from findings utilizing nicotine replacement. Results add to emerging data suggesting that smoking cessation interventions with varying mechanisms of action may result in different outcomes for premenopausal women based on gonadal hormones at quit date.     

Early-life social experiences in mice affect emotional behaviour and hypothalamic-pituitary-adrenal axis function

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.     

A systematic review of the impact of alcohol use disorders on HIV treatment outcomes, adherence to antiretroviral therapy and health care utilization

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.     

Treatment costs of hepatitis C infection among injection drug users in Canada, 2006-2026

Background

Canadian injection drug users (IDUs) are at high risk of hepatitis C virus infection (HCV). However, little is known about the costs associated with their HCV-related medical treatment. We estimated the medical costs of treating HCV-infected IDUs from 2006 to 2026.

Methods

We employed a Markov model of entry through birth or immigration to exposure-related behaviours or experiences, HCV infection, progression to HCV sequelae and mortality for active and ex-IDUs in Canada. We estimated direct and indirect treatment costs using data from the Ontario Case Costing Initiative (OCCI).

Result

Approximately 137,000 IDUs will suffer from HCV-related disease each year until 2026. Applying the OCCI cost data to the prevalence of HCV-related disease from 2006 to 2026 yielded an estimated cost of $3.96 billion CND to treat HCV-infected IDUs.

Conclusions

Substantial costs are associated with the treatment of HCV-related disease among Canadian IDUs. Given the lack of effective HCV prevention strategies in Canada, we must develop targeted evidence-based responses to prevent HCV transmission and ensure appropriate allocation of medical resources to meet the present and future treatment needs of HCV-infected IDUs.     

A qualitative evaluation of a peer-implemented overdose response pilot project in Gejiu, China

Background

A harm reduction NGO in southern Yunnan operating an emergency overdose response hotline service successfully reversed 76 overdoses through the administration of naloxone in one of the first interventions of its kind in China.

Method

To explore local understandings of risk factors related to overdose, assess ongoing barriers to overdose response, and solicit client input on how to further reduce opiate overdose mortality in Gejiu, the authors conducted qualitative interviews with 30 clients, including 15 individuals who received naloxone injections to reverse an overdose and 15 individuals who called the hotline in response to the overdose of a peer.

Results

Participants pointed to a number of local structural shifts in heroin use including the ageing of the opiate using population and drug mixing practises that contribute to the city's overdose toll. Concerns over medical professionals’ willingness to treat drug users, protection of confidentiality, and financial costs associated with treatment frequently cause drug users to avoid contact with the city's emergency service providers. Participants suggest directly distributing naloxone to clients as one strategy to further reduce overdose mortality.

Conclusion

The authors explore possible strategies, including targeted trainings and new partnerships with local hospitals, to further reduce opiate overdose mortality in this resource-poor setting.     

Development of a mucoadhesive nanoparticulate drug delivery system for a targeted drug release in the bladder

Purpose

Purpose of the present study was the development of a mucoadhesive nanoparticulate drug delivery system for local use in intravesical therapy of interstitial cystitis, since only a small fraction of drug actually reaches the affected site by conventional treatment of bladder diseases via systemic administration.

Methods

Chitosan-thioglycolic acid (chitosan-TGA) nanoparticles (NP) and unmodified chitosan NP were formed via ionic gelation with tripolyphosphate (TPP). Trimethoprim (TMP) was incorporated during the preparation process of NP. Thereafter, the mucoadhesive properties of NP were determined in porcine urinary bladders and the release of TMP among simulated conditions with artificial urine was evaluated.

Results

The particles size ranged from 183 nm to 266 nm with a positive zeta potential of +7 to +13 mV. Under optimized conditions the encapsulation efficiency of TMP was 37%. The adhesion of prehydrated chitosan-TGA NP on the urinary bladder mucosa under continuous urine voiding was 14-fold higher in comparison to unmodified chitosan NP. Release studies indicated a more sustained TMP release from covalently cross linked particles in comparison to unmodified chitosan-TPP NP over a period of 3 h in artificial urine at 37 °C.

Conclusion

Utilizing the method described here, chitosan-TGA NP might be a useful tool for local intravesical drug delivery in the urinary bladder.     

Validation of the Cannabis Expectancy Questionnaire (CEQ) in adult cannabis users in treatment

Background

Outcome expectancies are a key cognitive construct in the etiology, assessment and treatment of Substance Use Disorders. There is a research and clinical need for a cannabis expectancy measure validated in a clinical sample of cannabis users.

Method

The Cannabis Expectancy Questionnaire (CEQ) was subjected to exploratory (n = 501, mean age 27.45, 78% male) and confirmatory (n = 505, mean age 27.69, 78% male) factor analysis in two separate samples of cannabis users attending an outpatient cannabis treatment program. Weekly cannabis consumption was clinically assessed and patients completed the Severity of Dependence Scale-Cannabis (SDS-C) and the General Health Questionnaire (GHQ-28).

Results

Two factors representing Negative Cannabis Expectancies and Positive Cannabis Expectancies were identified. These provided a robust statistical and conceptual fit for the data. Internal reliabilities were high. Negative expectancies were associated with greater dependence severity (as measured by the SDS) and positive expectancies with higher consumption. The interaction of positive and negative expectancies was consistently significantly associated with self-reported functioning across all four GHQ-28 scales (Somatic Concerns, Anxiety, Social Dysfunction and Depression). Specifically, within the context of high positive cannabis expectancy, higher negative expectancy was predictive of more impaired functioning. By contrast, within the context of low positive cannabis expectancy, higher negative expectancy was predictive of better functioning.

Conclusions

The CEQ is the first cannabis expectancy measure to be validated in a sample of cannabis users in treatment. Negative and positive cannabis expectancy domains were uniquely associated with consumption, dependence severity and self-reported mental health functioning.     

Lessepsian migration and tetrodotoxin poisoning due to Lagocephalus sceleratus in the eastern Mediterranean

Background

The Suez Canal permits migration of fish from the Indo-Pacific Ocean to the Mediterranean Sea. This phenomenon (Lessepsian migration) has enabled poisonous fish species to colonize the Mediterranean Sea.

Objective

To report clinical tetrodotoxin poisoning after consumption of the Lessepsian immigrant fish Lagocephalus sceleratus caught on the Israeli coast of the eastern Mediterranean.

Case series

Thirteen patients aged 26-70 years were admitted after consuming L. sceleratus. Signs of toxicity appeared within 1 h. The main manifestations included vomiting, diarrhea, headache, paraesthesias, slurred speech, muscle weakness, dyspnea, hypertension, tachycardia, respiratory arrest, seizures and coma. Treatment was supportive, including mechanical ventilation (two patients). Patients recovered within 4 days. All fish were identified as L. sceleratus, a species known to contain tetrodotoxin.

Discussion

The diagnosis of tetrodotoxin poisoning was suggested by typical clinical manifestations together with temporal proximity to consumption of tetrodotoxin-containing fish. To the best of our knowledge, this is the first case series of tetrodotoxin poisoning reported from the eastern Mediterranean and due to L. sceleratus. Man made disruption of the ecological balance has resulted in the spread of tetrodotoxin-containing fish from the Indo-Pacific region to the Mediterranean Sea. Increased awareness is required to identify tetrodotoxin poisoning in an atypical fauna.     

Chronic hepatitis C virus infection and increases in viral load in a prospective cohort of young, HIV-uninfected injection drug users

Background

Chronic hepatitis C (HCV) infection, defined as persistent RNA (viral load) for at least 6 months, accounts for up to 50% of all cirrhosis, end-stage liver disease and liver cancer cases. Moreover, elevated HCV viral load is consistently associated with high infectivity and poor therapy response. This study aims to identify modifiable behavioral correlates both chronic HCV infection and increases in viral load over time among injection drug users (IDUs).

Methods

Cross-sectional and longitudinal analyses were performed using self-interview and serological data from a prospective cohort study (2002-2006) among young (age 18-35), HIV-negative, HCV therapy-naïve IDUs (n = 113) from metropolitan Chicago, Illinois, USA.

Results

After adjustment for age, gender and race/ethnicity, using drugs measured or mixed in someone else's syringe (odds ratio = 2.7, 95% confidence interval: 1.1, 6.7) was associated with chronic (n = 75, 66%) versus resolved (n = 38, 34%) HCV infection status. Among chronically-infected IDUs, injecting with a new, sterile syringe infrequently (<1/2 half the time when injecting) compared to frequently (1/2 the time or more when injecting) was associated with increases in viral load over time after adjusting for age, gender, race/ethnicity and time effects.

Conclusions

Reductions in risky injection-related practices among young IDUs may ameliorate both the burden of chronic HCV infection-related liver disease and elevated viral load-related poor treatment response.     

Quality of life under maintenance treatment with heroin versus methadone in patients with opioid dependence

Background

There is increasing evidence that health-related quality of life (HRQOL) is associated with a successful treatment and better outcome in opioid addiction. The aim of the present study was the longitudinal investigation of HRQOL in patients with severe opioid dependence, who were randomly assigned to four groups of medical and psychosocial treatment: heroin (diacetylmorphine) versus methadone and case management (CM) versus psychoeducation (PSE) respectively.

Methods

HRQOL (MSQoL) and physical health (OTI) were investigated in 938 subjects, who participated in the German multi-centre study examining the effects of heroin-assisted treatment in patients with severe opioid dependence. Data for the present analysis were taken from baseline and 12-month follow up.

Results

Under both forms of maintenance and psychosocial treatment HRQOL improved significantly during the observation period. HRQOL improvement under maintenance with heroin exceeded improvement under methadone, especially with regard to subjective physical health. HRQOL improvement was significantly associated with better expert-rated physical health. Further analyses showed significant better improvement of HRQOL in subjects treated with PSE compared with CM.

Conclusions

The advantage of heroin with regard to the improvement of HRQOL may be partially explained by a better improvement of physical health under maintenance with heroin compared with methadone, which highlights the importance of a comprehensive model of health care for patients with severe opioid dependence. Future studies need to investigate the benefits of PSE for patients in maintenance therapy.     

Systemic methotrexate induces spatial memory deficits and depletes cerebrospinal fluid folate in rats

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.