Progress towards eliminating tuberculosis in Ga West Municipality, Ghana: analysis of tuberculosis surveillance data, 2017.

OBJECTIVE: To assess the progress made towards the actualization of the 80% reduction in incident cases, monitor trends and to assess the quality of GWM TB surveillance data from 2012 to 2016. DESIGN: The study was descriptive secondary data analysis. DATA SOURCE: Tuberculosis cases recorded in the District Health Information Management Systems (DHIMS) and municipal TB registers. The Municipal TB Coordinator was interviewed for clarification on the data. A TB patient was defined as one who coughed persistently for two weeks or more. MAIN OUTCOME MEASURE: Trend of TB cases in Ga West Municipality. RESULTS: A total of 441 TB cases were registered of which 68.9% were smear positive. Males were (67%). Age group 35-44 years were the most affected (28.6%). The incidence rose from 21.5 (2012) to 41.6 (2015). The 2016 incidence was 40.7 (± 5.63) per 100,000 population. This is significantly different from the current national incidence of 156 (p < 0.05). Data was 95% complete. Discrepancies existed between data in registers compared to the DHIMS but were not statistically significant. CONCLUSION: The 80% reduction in incident cases target may not be attained by the GWM due to the rising number of incident cases. However, data quality is good. FUNDING: The study was funded by the authors.

Evaluation of viral haemorrhagic fever surveillance system with focus on Ebola virus disease, Bawku municipality- Upper East Region, Ghana, 2011-2015.

BACKGROUND: We evaluated the Viral haemorrhagic fever (VHF) surveillance system from 2011 to 2015 in the Bawku Municipality, Upper East region, Ghana to determine whether the goals of the surveillance system are being met and to assess the performance of the system attributes. DESIGN: Descriptive secondary data analysis. SETTING: Bawku Municipality. DATA SOURCE: Review VHF surveillance records, interviewed community-based surveillance volunteers (CBSVs) and reviewed vital events registers. We also assessed the system attributes by reviewing records and interviewing key stakeholders involved in VHF surveillance system with focus on Ebola using checklist and semi structured questionnaire developed based on the Centers for Disease Control and Prevention (CDC) guidelines. MAIN OUTCOME MEASURE: System attributes of the VHF surveillance system. RESULTS: Population under surveillance was 105,849. The system required detail information about suspected cases. However, it had a simple and clear standard case definitions, and was well integrated with the IDSR. There is a regular and timely flow of information. The system captured 155 suspected cases nationwide from 2011 to 2015 and all tested negative. Of these, Upper East Region reported 10 suspected cases including 4 suspected cases from Bawku Municipality. CONCLUSION: The VHF surveillance system achieved its objectives. However, poor data quality, inadequately trained surveillance officers, and inadequate financial support are threats to the effectiveness of the system. FUNDING: This work was supported by Ghana Field Epidemiology and Laboratory Training Program (GFELTP), University of Ghana.

Protracted cholera outbreak in the Central Region, Ghana, 2016.

OBJECTIVE: On 24th October 2016, the Central Regional Health Directorate received report of a suspected cholera outbreak in the Cape Coast Metropolis (CCM). We investigated to confirm the diagnosis, identify risk factors and implement control measures. DESIGN: We used a descriptive study followed by 1:2 unmatched case-control study. DATA SOURCE: We reviewed medical records, conducted active case search and contact tracing, interviewed case-patients and their contacts and conducted environmental assessment. Case-patients' stool samples were tested with point of care test kits (SD Bioline Cholera Ag 01/0139) and sent to the Cape Coast Teaching Hospital Laboratory for confirmation. MAIN OUTCOMES: Cause of outbreak, risk factors associated with spread of outbreak. RESULTS: Vibrio cholerae serotype Ogawa caused the outbreak. There was no mortality. Of 704 case-patients, 371(52.7%) were males and 55(7.8%) were aged under-five years. The median age was 23 years (interquartile range: 16-32 years). About a third 248(35.2%) of the case patients were aged 15-24 years. The University of Cape Coast subdistrict was the epicenter with 341(48.44%) cases. Compared to controls, cholera case-patients were more likely to have visited Cholera Treatment Centers (CTC) (aOR=12.1, 95%CI: 1.5-101.3), drank pipe-borne water (aOR=11.7, 95%CI: 3.3-41.8), or drank street-vended sachet water (aOR=11.0, 95%CI: 3.7-32.9). Open defecation and broken sewage pipes were observed in the epicenter. CONCLUSION: Vibrio cholerae serotype Ogawa caused the CCM cholera outbreak mostly affecting the youth. Visiting CTC was a major risk factor. Prompt case-management, contact tracing, health education, restricting access to CTC and implementing water sanitation and hygiene activities helped in the control. FUNDING: This work was supported by Ghana Field Epidemiology and Laboratory Training Program (GFELTP), University of Ghana.

Demographic and socio-cultural factors influencing contraceptive uptake among women of reproductive age in Tamale Metropolis, Northern Region, Ghana.

BACKGROUND: This study assessed some demographic and socio-cultural factors that influence contraceptive uptake among reproductive-aged women in Tamale Metropolis of the Northern Region, Ghana. DESIGN: This was a cross-sectional study conducted from February to March 2015. SETTING: All three sub Metropolis in Tamale. PARTICIPANTS: All community members and women of reproductive age (15-49 years). INTERVENTION: The study used cluster sampling to recruit women who were interviewed using a structured questionnaire. Nine focus group discussions (FGDs) were also held among community members who were purposively selected. MAIN OUTCOME MEASURES: contraceptive uptake (use of contraceptive). RESULTS: The mean age of the women was 26 years. The prevalence of contraceptive uptake among reproductive-age women was 36.8% (165/448). Women with secondary school education [AOR=4.4(95%CI:1.6-12.4)], and those in homes where decisions on having children were made by both partners [AOR=2.1(95%CI:1.1-04.42)] were more likely to use contraceptives. Unemployed women [AOR=0.3(95%CI:0.1-0.8)], women whose husbands were unaware of their contraceptive use [AOR=0.4(95%CI:0.2-0.9)] and those having a culture or religion that frowns on contraceptive use [AOR=0.4(95%CI:0.2-0.8)] were less likely to use contraceptive among women in the Tamale Metropolis. CONCLUSION: The study found a contraceptive prevalence rate (CPR) in Tamale Metropolis, Northern Ghana to be 36.8%. Education and living in a home where childbearing decisions are made together were identified as positive factors influencing contraceptive uptake. FUNDING: This work was funded by the authors.

Risk factors for ectopic pregnancy among pregnant women attending a tertiary healthcare facility in Accra, Ghana.

OBJECTIVE: To investigate risk factors for ectopic pregnancy among pregnant women attending the Korle-Bu Teaching Hospital, Accra, Ghana. METHODS: In an unmatched case-control study from September to November 2015, 104 women with ectopic pregnancy (cases) were compared with 208 women with intrauterine pregnancy (controls). Data were collected by interviewer-administered questionnaire and record review. Bivariable analysis was used to compare characteristics. Multivariate logistic regression was used to assess associations between risk factors and ectopic pregnancy. Adjusted odds ratios (aORs) and 95% confidence interval (CIs) were reported. RESULTS: Risk factors for ectopic pregnancy were being single (aOR, 5.5; 95% CI, 2.15-14.65), sexual debut at younger than 15 years (aOR, 36.4; 95% CI, 2.49-532.49), multiple sexual partners (aOR, 4.8; 95% CI, 1.76-13.36), previous instrumental evacuation of uterus (aOR, 5.8; 95% CI, 1.20-27.99); previous diagnosis of infertility (aOR, 6.1; 95% CI, 1.36-27.28), being uninsured (aOR, 11.8; 95% CI, 4.23-32.74), and condom use (aOR, 6.1; 95% CI, 1.36-27.28). CONCLUSION: Women who were single with early sexual intercourse, multiple partners, instrumental evacuation of the uterus, and diagnosis of infertility were at risk of ectopic pregnancy. Identification of these factors should facilitate early diagnosis and treatment of ectopic pregnancy.

Post-Ebola Syndrome among Ebola Virus Disease Survivors in Montserrado County, Liberia 2016.

INTRODUCTION: An increased number of survivors have emerged from the 2014 West African Ebola Virus Disease (EVD) epidemic. Post-Ebola Syndrome (PES) is a group of physical and psychological symptoms affecting EVD survivors. This study aimed to estimate the prevalence of PES among EVD survivors in Montserrado County, Liberia. METHOD: A cross-sectional study design was conducted to determine the prevalence of PES, types, onset, and duration among survivors. Survivors in Montserrado County were recruited using multistage sampling methods. Quantitative data was collected using semistructured questionnaire. Variables were collected on EVD survivors demographics, pre- and post-Ebola health history. RESULT: Prevalence of Post-Ebola Syndrome was estimated to be 90% (242/268). PES was experienced by 67% (162/242) females. PES occurred mainly in the adult population between ages 25-34, 35% (84/242). The commonest symptoms were reported from the following systems of the human body: neurological system (eyes problem, headache, sleep disorder, and unusual tiredness) and musculoskeletal system (abdominal pain, chest pain, and joints pains). The onset of PES occurred between the first 1-12 weeks after being discharged from a treatment unit. CONCLUSION: Prevalence of PES is high. Clinical care for survivors should be strengthened.

Contraceptive Methods Accessed in Volta Region, Ghana, 2009-2014.

INTRODUCTION: In 2016, Volta Region was one of the two regions in Ghana that recorded a high prevalence of teenage pregnancy, accounting for 15.5% of all adolescent pregnancies in the country. This study aimed to determine the prevalence of contraceptive methods accessed by person, place, and time in Volta Region, Ghana, 2009-2014. METHOD: We carried out a secondary analysis of contraceptive use data derived from the District Health Information Management System (DHIMS) 2 for Volta Region, between 2009 and 2014. We calculated proportions and described trends. RESULTS: Over the five-year period, there were 673,409 (75.0%) acceptors of family planning out of a total 897, 645 males and females of reproductive age. The proportion of family planning acceptors increased gradually from 18% in 2009 to 23% in 2014. Contraceptive methods were most commonly accessed by male and female between 20 and 29 years. The most common methods of contraceptives accessed were injectables among females accounting for about 70% and condoms accounting for over 90% among males. CONCLUSION: All the districts in Volta Region did not access contraceptives adequately. The Volta Regional Health Directorate should encourage and support research to ascertain factors influencing uptake of contraceptive methods in all the districts.

Meningitis Outbreak Caused by Vaccine-Preventable Bacterial Pathogens - Northern Ghana, 2016.

Bacterial meningitis is a severe, acute infection of the fluid surrounding the brain and spinal cord that can rapidly lead to death. Even with recommended antibiotic treatment, up to 25% of infected persons in Africa might experience neurologic sequelae (1). Three regions in northern Ghana (Upper East, Northern, and Upper West), located in the sub-Saharan "meningitis belt" that extends from Senegal to Ethiopia, experienced periodic outbreaks of meningitis before introduction of serogroup A meningococcal conjugate vaccine (MenAfriVac) in 2012 (2,3). During December 9, 2015-February 16, 2016, a total of 432 suspected meningitis cases were reported to health authorities in these three regions. The Ghana Ministry of Health, with assistance from CDC and other partners, tested cerebrospinal fluid (CSF) specimens from 286 patients. In the first 4 weeks of the outbreak, a high percentage of cases were caused by Streptococcus pneumoniae; followed by an increase in cases caused by Neisseria meningitidis, predominantly serogroup W. These data facilitated Ghana's request to the International Coordinating Group* for meningococcal polysaccharide ACW vaccine, which was delivered to persons in the most affected districts. Rapid identification of the etiologic agent causing meningitis outbreaks is critical to inform targeted public health and clinical interventions, including vaccination, clinical management, and contact precautions.

Outbreak of foodborne gastroenteritis in a senior high school in South-eastern Ghana: a retrospective cohort study.

BACKGROUND: On 4th February 2015, a group of Senior High School students from Fanteakwa district presented to the emergency unit of the district hospital with complaints of abdominal pain, vomiting and diarrhoea. All the students had eaten from a specific food vendor and had neither eaten any other common meal that day nor the previous day. A foodborne disease outbreak was suspected. We investigated to verify the outbreak, determine its magnitude, identify the source and implement control measures. METHODS: A retrospective cohort study was conducted. We reviewed medical records and interviewed patrons of the food vendor. We collected data on age, sex, signs and symptoms, date of illness onset, date of admission, date of discharge, treatments given and outcome. A case of foodborne disease was any person in the school with abdominal pain, vomiting and or diarrhoea from 4th to 11th February 2015 and had eaten from the food vendor. We conducted active case search to identify more cases. We conducted environmental assessment and collected clinical and food samples for laboratory testing. Descriptive and inferential statistical analyses were performed using Stata 12.0. RESULTS: A total of 68 cases were recorded giving overall attack rate of 35.79 % (68/190) with no death. Of these, 51.47 % (35/68) were males. Mean age of case-patients was 17.8 (standard deviation +/-1.62). The index case, a 17-year-old female student ate from the food vendor on 4th February at 9:00 am and fell ill at 3:40 pm later that day. Compared to those who ate other food items, students who drank water from container at the canteen were more likely to develop foodborne disease at statistically significant levels [RR = 2.6, 95 % CI = (2.11-3.15)]. Clostridium perfringens (C. perfringens) and Salmonella species (Salmonella spp) were isolated from water and stew respectively. Clinical features of case-patients were compatible with both organisms. CONCLUSION: A foodborne gastroenteritis outbreak occurred in a Senior High School in Fanteakwa District from 4th to 7th February 2015. The most probable aetiologic agent was C. perfringens with contaminated water at canteen as the vehicle of transmission. Concurrent Salmonella spp infection could not be ruled out. Rapid outbreak response helped in controlling the outbreak.

Assessing Lymphatic Filariasis Data Quality in Endemic Communities in Ghana, Using the Neglected Tropical Diseases Data Quality Assessment Tool for Preventive Chemotherapy.

BACKGROUND: The activities of the Global Programme for the Elimination of Lymphatic Filariasis have been in operation since the year 2000, with Mass Drug Administration (MDA) undertaken yearly in disease endemic communities. Information collected during MDA-such as population demographics, age, sex, drugs used and remaining, and therapeutic and geographic coverage-can be used to assess the quality of the data reported. To assist country programmes in evaluating the information reported, the WHO, in collaboration with NTD partners, including ENVISION/RTI, developed an NTD Data Quality Assessment (DQA) tool, for use by programmes. This study was undertaken to evaluate the tool and assess the quality of data reported in some endemic communities in Ghana. METHODS: A cross sectional study, involving review of data registers and interview of drug distributors, disease control officers, and health information officers using the NTD DQA tool, was carried out in selected communities in three LF endemic Districts in Ghana. Data registers for service delivery points were obtained from District health office for assessment. The assessment verified reported results in comparison with recounted values for five indicators: number of tablets received, number of tablets used, number of tablets remaining, MDA coverage, and population treated. Furthermore, drug distributors, disease control officers, and health information officers (at the first data aggregation level), were interviewed, using the DQA tool, to determine the performance of the functional areas of the data management system. FINDINGS: The results showed that over 60% of the data reported were inaccurate, and exposed the challenges and limitations of the data management system. The DQA tool is a very useful monitoring and evaluation (M&E) tool that can be used to elucidate and address data quality issues in various NTD control programmes.

The efficacy of prophylactic antibiotics in the management of children with kerosene-associated pneumonitis: a double-blind randomised controlled trial.

CONTEXT: Hydrocarbons, especially kerosene (paraffin), are the most common agents causing childhood poisoning in low and middle income countries (LMICs). Aspiration of kerosene causes an inflammatory sterile chemical pneumonitis, which may increase susceptibility to secondary lower respiratory tract bacterial infection. This study aimed to assess the efficacy of prophylactic antibiotics in the management of kerosene-associated pneumonitis in children and to identify risk factors associated with severity or outcome. METHODS: A double-blind placebo-controlled trial of prophylactic antibiotics in the management of kerosene-associated pneumonitis of children presenting to a referral hospital was performed from July 2010 to September 2011. Sequential children with a history of kerosene ingestion and mild respiratory illness were randomised to receive placebo or amoxicillin. Each child was followed-up at Day 3 and Day 5 post-ingestion. The primary outcome measure was the number of treatment failures in each group, defined as any child who deteriorated within this time, necessitating a change in treatment regimen. Secondary outcome measures were length of hospital stay and symptoms and signs at follow-up. RESULTS: Seventy-four patients were enrolled. Thirty-five (47%) received placebo and 39 (53%) active treatment. There was no significant difference in treatment failures between placebo (3/35, 9%; 95% CI, 3-22) and active (2/39, 5%; 95% CI, 1-17) groups (relative risk, 0.60; 95% CI, 0.11-3.37). The median length of hospital stay was identical (placebo 0.5 days; IQR, 0-1.0 and active 0.5 days; IQR, 0.5-1.0). Symptoms and signs at Days 3 and 5 post-ingestion were similar. The only significant risk factor for treatment failure was residence in formal housing. Clinical severity at presentation was similar for treatment successes and failures. CONCLUSION: Prophylactic antibiotics do not improve the outcome in children with mild respiratory illness after kerosene ingestion.

Transuranium radionuclide pollution in the waters of the La Maddalena National Marine Park.

Following the grounding and subsequent explosion, in October 2003, of a nuclear submarine in the waters of the La Maddalena National Marine Park, fears arose of possible radioactive leakages. However, isotopic analyses on algae showed that the gamma-ray emitting artificial radionuclides that one might expect to leak from a damaged nuclear reactor (such as U-235, I-131, Cs-137) were absent, and that U-238/U-234 activities were in equilibrium with values typical of sea water; this excluded any direct anthropogenic contamination as a result of the accident. We used alpha autoradiographic techniques to detect possible traces of transuranium radionuclides; 160 samples of algae, granites, sea urchins, gastropods, limpets, cuttlefish and jellyfish were collected from the area, as well as from other Mediterranean coastlines and the Baltic Sea. All samples were autoradiographed, and selected samples further analysed by alpha spectrometry. There were no alpha track concentrations above background levels in our control Mediterranean specimens. In the samples from the La Maddalena and Baltic areas two different track distributions were observed: --those homogeneously distributed over the surfaces examined; --groups (10 to over 500) of radially distributed alpha tracks (forming "star" bursts, or "hot spots") emanating from point sources. By comparing radionuclide activities measured by alpha spectroscopy with alpha track densities, we extrapolated Pu activities for all samples. About 74% of algae had Pu activities of less than 1 Bq/kg and 0.25 Bq/kg, 16% had accumulated Pu to levels between 1 and 2 Bq/kg, and a very few specimens had concentrations between 2 and 6 Bq/kg. Plots showed that alpha tracks and stars concentrate around the northern and eastern margins of the Rada (Basin) di Santo Stefano, sites facing the nuclear submarine base on the eastern shore of the island of Santo Stefano. What is the source of these nuclides: last century's atmospheric nuclear testing, Chernobyl or a local source? Their concentrated, extremely localised occurrence seems difficult to explain in terms of left-over worldwide nuclear pollution. A local source seems more plausible.

High-affinity neurotensin receptors in the rat nucleus accumbens: subcellular targeting and relation to endogenous ligand.

Neurotensin is present in selective mesolimbic dopaminergic projections to the nucleus accumbens (NAc) shell but also is synthesized locally in this region and in the motor-associated NAc core. We examined the electron microscopic immunolabeling of the high-affinity neurotensin receptor (NTR) and neurotensin in these subdivisions of rat NAc to determine the sites for receptor activation and potential regional differences in distribution. Throughout the NAc, NTR immunoreactivity was localized discretely within both neurons and glia. NTR-labeled neuronal profiles were mainly axons and axon terminals with diverse synaptic structures, which resembled dopaminergic and glutamatergic afferents, as well as collaterals of inhibitory projection neurons. These terminals had a significantly higher numerical density in the NAc core than in the shell but were prevalent in both regions, suggesting involvement in both motor and limbic functions. In each region, neurotensin was detected in a few NTR-immunoreactive axon terminals and in terminals that formed symmetric, inhibitory type synapses with NTR-labeled somata and dendrites. The NTR labeling, however, was not seen within these synapses and, instead, was localized to segments of dendritic and glial plasma membranes often near excitatory type synapses. Neuronal NTR immunoreactivity also was associated with cytoplasmic tubulovesicles and nuclear membranes. Our results suggests that, in the NAc shell and core, NTR is targeted mainly to presynaptic sites, playing a role in the regulated secretion and/or retrograde signaling in diverse, neurotransmitter-specific neurons. The findings also support a volume mode of neurotensin actions, specifically affecting excitatory transmission through activation of not only axonal but also dendritic and glial NTR.

Early results of an objective olfactometer.

Although many people comment on their ability or inability to smell an odour, the accurate measurement of olfaction remains an elusive goal. Currently, there are no instruments available to objectively measure olfaction. This article outlines the design and early test results of a low cost, computer-based olfactometer which uses the frequency content of evoked potentials to quantify a subject's response to an olfactory stimulus. Clinical trials have been undertaken to establish the validity of the olfactometer and over a thousand tests have been carried out. Early results suggest that the methodology employed is appropriate and could be developed to enable a commercial olfactometer to be produced.

Ultrastructural immunocytochemical localization of the dopamine D2 receptor within GABAergic neurons of the rat striatum.

Classical antipsychotics, which block dopamine (DA) D2 receptors, showing intrastriatal variation in their effectiveness in modulating GABAergic function. To determine the cellular basis for such differences, we examined the electron microscopic immunocytochemical labeling of D2 receptors and GABA in the dorsolateral caudate-putamen (CPn) and the nucleus accumbens (Acb) shell. In both regions, peroxidase reaction product and gold-silver deposits representing D2 receptor immunoreactivity (D2-IR) and GABA immunoreactivity (GABA-IR), respectively, were detected in dendrites and perikarya having characteristics of either spiny projection neurons or aspiny interneurons. Some perikarya in both regions are dually labeled with D2-IR and GABA-IR. Neurons axon terminals in each region also contained one or both markers. However, there were notable regional differences in the immunolabeling patterns. In the CPn, D2-IR was more commonly seen in dendrites/spines than in axon terminals, and proportionally more dendrites were dually labeled than in the Acb. In the Acb shell, D2-IR was detected with similar frequency in terminals and dendrites/spines, but more terminals co-localized D2-IR and GABA-IR in this region compared with the CPn. These results provide the first ultrastructural evidence for direct D2-mediated effects of DA on striatal GABAergic neurons. They further suggest that modulation of GABAergic neurons by DA acting at D2 receptors may be relatively more postsynaptic in the CPn, but more presynaptic in the Acb shell.

Modifications of the Brandel Superfusion 600 system and other revisions in superfusion technique improve the measurement of endogenous dopamine release in vitro.

The Brandel Superfusion 600 is an automated system designed for the simultaneous measurement of neurotransmitter release from tissue slices from six chambers. In optimizing a technique for the measurement of endogenous dopamine (DA) with this system, a number of factors were identified which affected adversely both the accuracy and the precision of within and between experiments. These factors included bubbles in the perfusion chamber, an apparent loss of tissue viability during preparation of the slices, depletion of DA stores after multiple stimulations and degradation of DA in the perfusate after collection. The method was substantially improved with modifications in the Superfusion 600 system and by the addition of high Mg2+ to the preparation buffer. The addition of tyrosine to the perfusion buffer and the prevention of analyte degradation with antioxidant agents also improved accuracy and precision of measurements.

Ultrastructural immunocytochemical localization of neurotensin and the dopamine D2 receptor in the rat nucleus accumbens.

The neuroleptic-like effects of neurotensin (NT) are thought to be due to interactions with dopamine (DA) acting primarily at D2 receptors within the nucleus accumbens septi (Acb). Using electron microscopic dual labeling immunocytochemistry, we sought to demonstrate cellular substrates for functional interactions involving NT and DA D2 receptors in the adult rat Acb. Peroxidase reaction product representing D2 receptor-like immunoreactivity (D2-LI) was seen along membranes of Golgi lamellae and multivesicular bodies of perikarya containing immunogold labeling representing NT-LI. Dually labeled somata usually contained highly indented nuclei, a characteristic of aspiny neurons. Dendrites also occasionally colocalized the two immunomarkers. Other somata, dendrites, and all axon terminals were singly labeled with either NT-LI or D2-LI. In distinct sets of terminals, NT-LI was commonly associated with large, dense-cored vesicles, whereas D2-LI was found along the plasmalemma and over nearby small clear vesicles. Each type of terminal comprised approximately 20% of synaptic input to NT-immunoreactive dendrites. Similar proportions of terminals containing NT-LI or D2-LI contacted unlabeled (approximately 55%) or NT-labeled (approximately 35%) dendrites and, occasionally, were observed converging onto common dendrites. Terminals containing NT-LI or D2-LI also were often closely apposed. These findings provide the first ultrastructural evidence that: (1) NT and D2 receptors are colocalized in aspiny neurons and dendrites, (2) NT may produce a direct postsynaptic effect on neurons receiving input from terminals which are presynaptically modulated by DA via D2 receptors, and (3) NT and DA acting at D2 receptors may interact through presynaptic modulation of common axon terminals.

Protection against methamphetamine-induced neurotoxicity to neostriatal dopaminergic neurons by adenosine receptor activation.

Methamphetamine (METH)-induced neurotoxicity to nigrostriatal dopaminergic neurons in experimental animals appears to have a glutamatergic component because blockade of N-methyl-D-aspartate receptors prevents the neuropathologic consequences. Because adenosine affords neuroprotection against various forms of glutamate-mediated neuronal damage, the present studies were performed to investigate whether adenosine plays a protective role in METH-induced toxicity. METH-induced decrements in neostriatal dopamine content and tyrosine hydroxylase activity in mice were potentiated by concurrent treatment with caffeine, a nonselective adenosine antagonist that blocks both A1 and A2 adenosine receptors. In contrast, chronic treatment of mice with caffeine through their drinking water for 4 weeks, which increased the number of adenosine A1 receptors in the neostriatum and frontal cortex, followed by drug washout, prevented the neurochemical changes produced by the treatment of mice with METH treatment. In contrast, this treatment did not prevent 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced dopaminergic neurotoxicity. Furthermore, concurrent administration of cyclopentyladenosine, an adenosine A1 receptor agonist, attenuated the METH-induced neurochemical changes. This protection by cyclopentyladenosine was blocked by cyclopentyltheophylline, an A1 receptor antagonist. These results indicate that activation of A1 receptors can protect against METH-induced neurotoxicity in mice.