Warming underpins community turnover in temperate freshwater and terrestrial communities.

Rising temperatures are leading to increased prevalence of warm-affinity species in ecosystems, known as thermophilisation. However, factors influencing variation in thermophilisation rates among taxa and ecosystems, particularly freshwater communities with high diversity and high population decline, remain unclear. We analysed compositional change over time in 7123 freshwater and 6201 terrestrial, mostly temperate communities from multiple taxonomic groups. Overall, temperature change was positively linked to thermophilisation in both realms. Extirpated species had lower thermal affinities in terrestrial communities but higher affinities in freshwater communities compared to those persisting over time. Temperature change's impact on thermophilisation varied with community body size, thermal niche breadth, species richness and baseline temperature; these interactive effects were idiosyncratic in the direction and magnitude of their impacts on thermophilisation, both across realms and taxonomic groups. While our findings emphasise the challenges in predicting the consequences of temperature change across communities, conservation strategies should consider these variable responses when attempting to mitigate climate-induced biodiversity loss.

The health and economic burden of dust pollution in the textile industry of Faisalabad, Pakistan.

BACKGROUND: Exposure to dust in textile mills adversely affects workers' health. We collected epidemiological data on textile workers suffering from respiratory diseases and assessed work absence associated with illnesses in Faisalabad, Pakistan. METHODS: We recruited 206 workers using multistage sampling from 11 spinning mills in Faisalabad, Pakistan. The data were collected using 2-week health diaries and face-to-face interviews. The data pertains to socio-demographics, occupational exposures, the state of the workers' health, and other attributes. A theoretical framework of the health production function was used to estimate the relationship between cotton dust exposure and respiratory illnesses. We also estimated functional limitations (e.g., work absence) associated with dust exposure. STATA 12 was used to calculate descriptive statistics, an ordered probit for byssinosis, a probit model for chronic cough, and three complementary log-log models for blood phlegm, bronchitis, and asthma to measure dose-response functions. A Tobit model was used to measure the sickness absence function. RESULTS: We found that cotton dust exposure causes a significant health burden to workers, such as cough (35%), bronchitis (17%), and different grades of byssinosis symptoms (22%). The regression analysis showed that smoking cigarettes and working in dusty sections were the main determinants of respiratory diseases. Dusty work sections also cause illness-related work absences. However, the probability of work absence decreases with the increased use of face masks. CONCLUSION: The study's findings imply the significance of promoting occupational safety and health culture through training and awareness among workers or implementing the use of safety gadgets. Promulgating appropriate dust standards in textile mills is also a need of the hour.

Global change impacts on bird biodiversity in South Asia: potential effects of future land-use and climate change on avian species richness in Pakistan.

Evaluating the impact of future changes in land-use and climate on species communities, especially species richness, is one of the most important challenges of current research in ecology and conservation. The impact of environmental changes on species richness depends on its sensitivity (i.e., how strongly a given level of change influences the ecological community) and its exposure (i.e., the amount of change that occurs). To examine the sensitivity, exposure, and potential impact of future environmental conditions on bird communities, we compiled data on bird species richness for Pakistan-a neglected region in macro- or country-scale studies. Since bird species richness strongly varies across seasons due to the seasonal occurrence of migratory species in winter, we compared both wintering (migratory plus resident species) and breeding (resident species only) bird richness. We found breeding and wintering species richness to be sensitive to temperature, precipitation and rainfed cropland by being positively related to these factors. Exposure varied regionally, with projected temperature changes being most profound in northern regions while the strongest projected precipitation changes occurred in central and southern regions. The projected impact of future environmental change were highly heterogeneous across the country and differed between the wintering and breeding communities. Overall, the most negatively impacted region was projected to be the Khyber Pakhtunkha province in the North of Pakistan, due to reductions in precipitation and rainfed cropland, resulting in a projected negative impact, especially on wintering species richness. By highlighting the regional and seasonal bird communities most at risk, our findings provide useful information for policy makers to help devise new policies for mitigating negative impacts of future environmental changes on birds within Pakistan.

Using eDNA to understand predator-prey interactions influenced by invasive species.

Invasive predatory species may alter population dynamic processes of their prey and impact biological communities and ecosystem processes. Revealing biotic interactions, however, including the relationship between predator and prey, is a difficult task, in particular for species that are hard to monitor. Here, we present a case study that documents the utility of environmental DNA analysis (eDNA) to assess predator-prey interactions between two invasive fishes (Lepomis gibbosus, Pseudorasbora parva) and two potential amphibian prey species, (Triturus cristatus, Pelobates fuscus). We used species-specific TaqMan assays for quantitative assessment of eDNA concentrations from water samples collected from 89 sites across 31 ponds during three consecutive months from a local amphibian hotspot in Germany. We found a negative relationship between eDNA concentrations of the predators (fishes) and prey (amphibians) using Monte-Carlo tests. Our study highlights the potential of eDNA application to reveal predator-prey interactions and confirms the hypothesis that the observed local declines of amphibian species may be at least partly caused by recently introduced invasive fishes. Our findings have important consequences for local conservation management and highlight the usefulness of eDNA approaches to assess ecological interactions and guide targeted conservation action.

The role of thermal tolerance in determining elevational distributions of four arthropod taxa in mountain ranges of southern Asia.

Understanding the role of thermal tolerances in determining species distributions is important for assessing species responses to climate change. Two hypotheses linking physiology with species distributions have been put forward-the climatic variability hypothesis and the climatic extreme hypothesis. The climatic variability hypothesis predicts the selection of individuals with broad thermal tolerance in more variable climatic conditions and the climatic extreme hypothesis predicts the selection of individuals with extreme thermal tolerance values under extreme climatic conditions. However, no study has tested the predictions of these hypotheses simultaneously for several taxonomic groups along elevational gradients. Here, we related experimentally measured critical thermal maxima, critical thermal minima and thermal tolerance breadths for 15,187 individuals belonging to 116 species of ants, beetles, grasshoppers, and spiders from mountain ranges in central and northern Pakistan to the limits and breadths of their geographic and temperature range. Across all species and taxonomic groups, we found strong relationships between thermal traits and elevational distributions both in terms of geography and temperature. The relationships were robust when repeating the analyses for ants, grasshoppers, and spiders but not for beetles. These results indicate a strong role of physiology in determining elevational distributions of arthropods in Southern Asia. Overall, we found strong support for the climatic variability hypothesis and the climatic extreme hypothesis. A close association between species' distributional limits and their thermal tolerances suggest that in case of a failure to adapt or acclimate to novel climatic conditions, species may be under pressure to track their preferred climatic conditions, potentially facing serious consequences under current and future climate change.

Linking human impacts to community processes in terrestrial and freshwater ecosystems.

Human impacts such as habitat loss, climate change and biological invasions are radically altering biodiversity, with greater effects projected into the future. Evidence suggests human impacts may differ substantially between terrestrial and freshwater ecosystems, but the reasons for these differences are poorly understood. We propose an integrative approach to explain these differences by linking impacts to four fundamental processes that structure communities: dispersal, speciation, species-level selection and ecological drift. Our goal is to provide process-based insights into why human impacts, and responses to impacts, may differ across ecosystem types using a mechanistic, eco-evolutionary comparative framework. To enable these insights, we review and synthesise (i) how the four processes influence diversity and dynamics in terrestrial versus freshwater communities, specifically whether the relative importance of each process differs among ecosystems, and (ii) the pathways by which human impacts can produce divergent responses across ecosystems, due to differences in the strength of processes among ecosystems we identify. Finally, we highlight research gaps and next steps, and discuss how this approach can provide new insights for conservation. By focusing on the processes that shape diversity in communities, we aim to mechanistically link human impacts to ongoing and future changes in ecosystems.

A DNA barcode survey of insect biodiversity in Pakistan.

Although Pakistan has rich biodiversity, many groups are poorly known, particularly insects. To address this gap, we employed DNA barcoding to survey its insect diversity. Specimens obtained through diverse collecting methods at 1,858 sites across Pakistan from 2010-2019 were examined for sequence variation in the 658 bp barcode region of the cytochrome c oxidase 1 (COI) gene. Sequences from nearly 49,000 specimens were assigned to 6,590 Barcode Index Numbers (BINs), a proxy for species, and most (88%) also possessed a representative image on the Barcode of Life Data System (BOLD). By coupling morphological inspections with barcode matches on BOLD, every BIN was assigned to an order (19) and most (99.8%) were placed to a family (362). However, just 40% of the BINs were assigned to a genus (1,375) and 21% to a species (1,364). Five orders (Coleoptera, Diptera, Hemiptera, Hymenoptera, Lepidoptera) accounted for 92% of the specimens and BINs. More than half of the BINs (59%) are so far only known from Pakistan, but others have also been reported from Bangladesh (13%), India (12%), and China (8%). Representing the first DNA barcode survey of the insect fauna in any South Asian country, this study provides the foundation for a complete inventory of the insect fauna in Pakistan while also contributing to the global DNA barcode reference library.

Does habitat heterogeneity influence taxonomic richness and abundance? A case study from a terrestrial protected area in Abu Dhabi, United Arab Emirates.

Biodiversity is under enormous pressure from multiple threats including climate change, land use change, habitat alterations and hunting pressure. One way to ease this pressure on biodiversity and to mitigate the effects of above-mentioned threats, is to establish protected areas. Importance of protected increases many folds in regions that are considered as biodiversity poor regions i.e. deserts. Protected areas have long been a major pillar of biodiversity conservation strategies; the Houbara Protected Area (HPA) is one of the 13 terrestrial protected areas in Abu Dhabi Emirate officially declared in 2017. However, no information regarding the status of biodiversity in the HPA has been communicated to the research fraternity. During the present study, surveys were conducted to fill this gap. The survey area was divided in to 50 grids of 5 × 5 km2 and monitoring surveys were undertaken from January to December 2016. A total of 14 bi-monthly to monthly surveys were conducted within HPA and 196 species of different taxonomical groups were recorded. A year-long survey yielded highly diversified fauna and flora from 19 different habitat types (H) 1.32, (E) 2.28, Shannon Diversity Index). We looked at the influence of habitat breadth and temperature on the species richness and abundance, results shows that in desert setup heterogeneity of habitat is not an important factor in maintaining the biodiversity as total number of individuals as well as species were similar in the grids that have different number of habitat types (df = 34.3, t = -0.472, P = 0.640). However, we did find a positive impact of mean monthly temperature on species richness (df = 154, t = 2.53, P = 0.012). Our study highlights the importance of temperature in driving species abundance and richness in protected area. Abundance and species richness are similar in protected areas indicating that protection is allowing species to explore the heterogenous habitats. Overall, we can conclude that protection is beneficial for species.

Combining environmental DNA and species distribution modeling to evaluate reintroduction success of a freshwater fish.

Active species reintroduction is an important conservation tool when aiming for the restoration of biological communities and ecosystems. The effective monitoring of reintroduction success is a crucial factor in this process. Here, we used a combination of environmental DNA (eDNA) techniques and species distribution models (SDMs) to evaluate the success of recent reintroductions of the freshwater fish Alburnoides bipunctatus in central Germany. We built SDMs without and with eDNA presence data to locate further suitable reintroduction sites and potentially overlooked populations of the species. We successfully detected eDNA of A. bipunctatus at all reintroduction sites, as well as several adjacent sites mostly in downstream direction, which supports the success of reintroduction efforts. eDNA-based species detection considerably improved SDMs for A. bipunctatus, which allowed to identify species presence in previously unknown localities. Our results confirm the usefulness of eDNA techniques as standard tool to monitor reintroduced fish populations. We propose that combining eDNA with SDMs is a highly effective approach for long-term monitoring of reintroduction success in aquatic species.

Pathways to care for patients in Pakistan experiencing signs or symptoms of breast cancer.

Multiple social and financial barriers exist to breast cancer detection in Pakistan, which may cause a delay in seeking care and the final diagnosis. This analytical study documents the pathways and time courses associated with referral to diagnostic centres to evaluate the clinical signs and symptoms of breast cancer. This report also verifies the association between socio-demographic and clinical indicators concerning the length of time spent before reaching diagnostic facilities. A purposive sample of 200 patients was selected from two tertiary care hospitals in Lahore, Pakistan, for the interviews. Descriptive statistics (that is, percentages, frequencies, and measures of central tendencies) and a multiple linear regression model were used to achieve the study objectives. The descriptive model showed 31-128 days interval between a patient's awareness of a clinical sign or symptom and receiving care. The healthcare system, including traditional healers, took from 7 to 194 days, and the time to diagnosis ranged from 15 to 30 days. Pain severity, larger tumour size, lack of clinical improvement, and the desire to obtain better treatment were reasons given for seeking care, but lack of awareness and fear of financial burden related to accessing healthcare facilities were identified as barriers. Moreover, socio-demographic and other predictive clinical factors were potentially associated with and substantially influenced the likelihood of the increased length of breast cancer patients' time to reach diagnostic centres. In conclusion, referrals by multiple healthcare providers, especially traditional healers and general practitioners, was a significant predictor for delay in diagnosis. Therefore, increased awareness and a responsive healthcare system may reduce the time from the recognition of symptoms to the early detection of breast cancer among women, thus improving outcomes in a developing country.

Testing the heat dissipation limitation hypothesis: basal metabolic rates of endotherms decrease with increasing upper and lower critical temperatures.

Metabolic critical temperatures define the range of ambient temperatures where endotherms are able to minimize energy allocation to thermogenesis. Examining the relationship between metabolic critical temperatures and basal metabolic rates (BMR) provides a unique opportunity to gain a better understanding of how animals respond to varying ambient climatic conditions, especially in times of ongoing and projected future climate change. We make use of this opportunity by testing the heat dissipation limit (HDL) theory, which hypothesizes that the maximum amount of heat a species can dissipate constrains its energetics. Specifically, we test the theory's implicit prediction that BMR should be lower under higher metabolic critical temperatures. We analysed the relationship of BMR with upper and lower critical temperatures for a large dataset of 146 endotherm species using regression analyses, carefully accounting for phylogenetic relationships and body mass. We show that metabolic critical temperatures are negatively related with BMR in both birds and mammals. Our results confirm the predictions of the HDL theory, suggesting that metabolic critical temperatures and basal metabolic rates respond in concert to ambient climatic conditions. This implies that heat dissipation capacities of endotherms may be an important factor to take into account in assessments of species' vulnerability to climate change.

Human-modified biogeographic patterns and conservation in game birds: The dilemma of the black francolin (Francolinus francolinus, Phasianidae) in Pakistan.

The ever-increasing human-mediated wildlife reshuffling is raising concern for the conservation of biodiversity. The loss of biological distinctiveness among regions lessens the genetic diversity and consequently the evolutionary potential of local biotas to tackle present-day global change and human disturbance. This process may be sometimes cryptic unless investigated by means of a molecular approach. In this respect, game birds are a paradigmatic case. The black francolin (Francolinus francolinus, Phasianidae) is a medium-sized galliform whose distribution range stretches from Cyprus to the Gulf of Bengal. Six morphologic subspecies are known, with three of which occurring in Pakistan, where the species is heavily hunted and used as pet for chirping competitions. We genotyped 98 samples (feathers) at both the entire mitochondrial DNA Control Region gene and nine microsatellite loci to get a deeper insight into the genetic diversity of the black francolin in Pakistan in order to offer cogent recommendations for its conservation management. We identified several mtDNA lineages that were consistent with the currently described subspecies/taxonomy whose pattern of co-occurrence is compatible with the geological history and the faunal movement routes of the region under study. However, the biparentally inherited microsatellites returned a quite discordant picture of an extensive, sex-biased genetic mixing due to the intensive relocations of already overharvested male individuals for chirping competitions. Our results indicated that the genetic integrity of the black francolin in Pakistan could be seriously at risk and call for monitoring and limiting its trade other than enhancing the public awareness of the importance of local biodiversity resources.

Comparison of two public sector tertiary care hospitals' management in reducing direct medical cost burden on breast carcinoma patients in Lahore, Pakistan.

PURPOSE: Breast cancer is one of the major causes of death incurring highest morbidity and mortality amongst women of Pakistan. The purpose of this study was to assess and compare the role of two public sector tertiary care hospitals' management in reducing out of pocket (OOP) expenses on direct medical costs borne by breast carcinoma patients' household from diagnosis through treatment. Moreover, the study intended to explore the reasons of opting private diagnostic facilities by the said patients during the services taken from the foresaid tertiary care centers. METHODS: A purposive sample of 164 primary breast carcinoma patients was recruited for data collection of this cross-sectional study. Face to face interviews and semistructured questionnaires were adopted as method of data gathering tools. Major cost components of direct medical costs were used to compare the financial strain on the patients' households of both targeted hospitals. In addition, information was collected regarding the reasons of opting private diagnostic centers for investigations. Frequency, percentages, median and inter quartile range (IQR) were calculated for the data. Non-parametric variables were compared using the Mann-Whitney U test. RESULTS: It was observed that overall direct medical cost borne by the breast carcinoma patients' households in Jinnah hospital (median US$1153.93 / Rs. 118,589) was significantly higher than Mayo hospital (median US$427.93 /Rs. 43,978), p<0.001; r=0.623. Moreover, spending on almost all of the components of direct medical cost were found smaller in case of Mayo hospital's patients as compared to Jinnah hospital. CONCLUSION: This study indicates that OOP direct medical cost burden was found considerably less in Mayo hospital as compared to Jinnah hospital. The OOP expenditures on chemotherapy were overwhelmingly high. However, high spending on privately opted investigations procedures was the common issue of the patients under treatment in both hospitals.

Household costs of breast cancer morbidity: An empirical assessment from Pakistan.

PURPOSE: Health care costs attributable to breast cancer are substantial. In countries with high poverty, lack of public health infrastructure and low availability of health insurance, the economic burden of disease does not accrue solely to health care, but also on patients and their families. This study was conducted to explore the cost burden (i.e. direct medical costs, direct non-medical costs and indirect non-medical costs) incurred by breast cancer patients and their families over diagnosis and treatment. METHODS: Data was collected from 200 breast cancer patients at two hospitals in Lahore, provincial capital of Punjab, Pakistan, by employing purposive sampling technique. Costs were aggregated into three categories and compared with each other as per their weightage. RESULTS: The study found that direct medical care (US$ 1262.18/ Local currency (PKR) 129,717) is the largest expense, followed by direct non-medical (US$ 310.88 / PKR 31,950) and indirect non-medical costs (US$ 273.38 / PKR 28,096). CONCLUSIONS: The results of this study provide rich insight into the financial burden borne by households of breast cancer patients and suggest policy implications.

Does metabolism constrain bird and mammal ranges and predict shifts in response to climate change?

Mechanistic approaches for predicting the ranges of endotherms are needed to forecast their responses to environmental change. We test whether physiological constraints on maximum metabolic rate and the factor by which endotherms can elevate their metabolism (metabolic expansibility) influence cold range limits for mammal and bird species. We examine metabolic expansibility at the cold range boundary (MECRB) and whether species' traits can predict variability in MECRB and then use MECRB as an initial approach to project range shifts for 210 mammal and 61 bird species. We find evidence for metabolic constraints: the distributions of metabolic expansibility at the cold range boundary peak at similar values for birds (2.7) and mammals (3.2). The right skewed distributions suggest some species have adapted to elevate or evade metabolic constraints. Mammals exhibit greater skew than birds, consistent with their diverse thermoregulatory adaptations and behaviors. Mammal and bird species that are small and occupy low trophic levels exhibit high levels of MECRB. Mammals with high MECRB tend to hibernate or use torpor. Predicted metabolic rates at the cold range boundaries represent large energetic expenditures (>50% of maximum metabolic rates). We project species to shift their cold range boundaries poleward by an average of 3.9° latitude by 2070 if metabolic constraints remain constant. Our analysis suggests that metabolic constraints provide a viable mechanism for initial projections of the cold range boundaries for endotherms. However, errors and approximations in estimating metabolic constraints (e.g., acclimation responses) and evasion of these constraints (e.g., torpor/hibernation, microclimate selection) highlight the need for more detailed, taxa-specific mechanistic models. Even coarse considerations of metabolism will likely lead to improved predictions over exclusively considering thermal tolerance for endotherms.

Metabolic heat production and thermal conductance are mass-independent adaptations to thermal environment in birds and mammals.

The extent to which different kinds of organisms have adapted to environmental temperature regimes is central to understanding how they respond to climate change. The Scholander-Irving (S-I) model of heat transfer lays the foundation for explaining how endothermic birds and mammals maintain their high, relatively constant body temperatures in the face of wide variation in environmental temperature. The S-I model shows how body temperature is regulated by balancing the rates of heat production and heat loss. Both rates scale with body size, suggesting that larger animals should be better adapted to cold environments than smaller animals, and vice versa. However, the global distributions of ∼9,000 species of terrestrial birds and mammals show that the entire range of body sizes occurs in nearly all climatic regimes. Using physiological and environmental temperature data for 211 bird and 178 mammal species, we test for mass-independent adaptive changes in two key parameters of the S-I model: basal metabolic rate (BMR) and thermal conductance. We derive an axis of thermal adaptation that is independent of body size, extends the S-I model, and highlights interactions among physiological and morphological traits that allow endotherms to persist in a wide range of temperatures. Our macrophysiological and macroecological analyses support our predictions that shifts in BMR and thermal conductance confer important adaptations to environmental temperature in both birds and mammals.

Global variation in thermal tolerances and vulnerability of endotherms to climate change.

The relationships among species' physiological capacities and the geographical variation of ambient climate are of key importance to understanding the distribution of life on the Earth. Furthermore, predictions of how species will respond to climate change will profit from the explicit consideration of their physiological tolerances. The climatic variability hypothesis, which predicts that climatic tolerances are broader in more variable climates, provides an analytical framework for studying these relationships between physiology and biogeography. However, direct empirical support for the hypothesis is mostly lacking for endotherms, and few studies have tried to integrate physiological data into assessments of species' climatic vulnerability at the global scale. Here, we test the climatic variability hypothesis for endotherms, with a comprehensive dataset on thermal tolerances derived from physiological experiments, and use these data to assess the vulnerability of species to projected climate change. We find the expected relationship between thermal tolerance and ambient climatic variability in birds, but not in mammals-a contrast possibly resulting from different adaptation strategies to ambient climate via behaviour, morphology or physiology. We show that currently most of the species are experiencing ambient temperatures well within their tolerance limits and that in the future many species may be able to tolerate projected temperature increases across significant proportions of their distributions. However, our findings also underline the high vulnerability of tropical regions to changes in temperature and other threats of anthropogenic global changes. Our study demonstrates that a better understanding of the interplay among species' physiology and the geography of climate change will advance assessments of species' vulnerability to climate change.

Mitochondrial DNA diversity in Francolinus pondicerianus interpositus (grey francolin, Galliformes) from Pakistan.

Francolinus pondicerianus interpositus (grey francolin, Galliformes) is the only francolin present in the Suleiman Range (central Pakistan), one of the poorest and least developed areas in Pakistan. As a game bird, the francolin is an important income source for the region, but no demographic data are available. Therefore, the aim of this work was to study the polymorphism pattern of the Control Region gene (mitochondrial DNA, mtDNA), in order to obtain some initial information about genetic diversity, possible structure and demographic dynamics in this population. In 29 individuals captured in four sampling areas in the western and the eastern Suleiman Range, we detected nine polymorphic sites in a 511 bp fragment of the mtDNA Control Region gene, resulting in seven haplotypes. Haplotype (h = 0.818 ± 0.032) and nucleotide diversity (π % = 0.308 ± 0.210) values suggested a large population size and a low divergence among the haplotypes. AMOVA (Φ(ST) = 0.005; P = 0.352) did not detect any significant differences among the western and eastern populations; therefore, specimens of both sampled areas could be considered as drawn from a single population. The observed distribution of pairwise mismatches was bimodal, revealing significant departure from a growing-decreasing population model (P = 0.030); these results would point to a demographic equilibrium. Tribal control of hunting might provide an explanation for this situation, but future overhunting would threaten the survival of this population.

Orphanin FQ/nociceptin blocks cocaine-induced behavioral sensitization in rats.

RATIONALE: Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL-1) receptor, shows similarities to dynorphin A (1-17) in structure and functions. Dynorphin and other kappa opioid receptor agonists have been shown to block cocaine sensitization. OBJECTIVE: The present study was designed to examine the ability of OFQ/N to block cocaine-induced behavioral sensitization. METHODS: Rats were habituated to testing chambers for 1 h, injected with artificial cerebrospinal fluid (aCSF) or OFQ/N (15 nmol) followed by saline or cocaine (20 mg/kg) and locomotor activity was measured for a further 1 h. Rats were treated similarly for the next 2 days except the dose of OFQ/N was doubled on each subsequent day. Rats were then challenged with cocaine (7.5 mg/kg) in the absence of OFQ/N on day 8. The specificity of OFQ/N's action was examined in the presence of J-113397 (30 nmol), an ORL-1 receptor antagonist. The ability of OFQ/N to block the context-independent component of cocaine sensitization was also tested wherein rats were treated in their home cages on days 1-3. Finally, the effect of intra-VTA OFQ/N administration on cocaine sensitization was examined. RESULTS: Sensitization did not develop in rats repeatedly treated with OFQ/N, via either route of administration, prior to cocaine administration on days 1-3. The inhibitory effect of OFQ/N was not dependent on context and was blocked by pretreatment with J-113397. CONCLUSION: Our results indicate that OFQ/N blocks cocaine-induced behavioral sensitization through activation of the ORL-1 receptor and that the VTA may be one of the substrates for this action of OFQ/N.