Pharmacology, Toxicology and Environmental Health Commons^™

Ecological And Anthropogenic Influences On A Sentinel Species' Gut Microbiome, Carson E. Black

All Master's Theses

Central and South American primates face augmented challenges due to increased rates of forest fragmentation. Among these challenges are implications on the nonhuman primate gut microbiome. Wild Argentine black and gold howler monkeys (Alouatta caraya) are listed as “least concern” with a population that is decreasing. Despite their propensity to occupy habitats with varying degrees of degradation and disturbance, they are not immune from the stressors that forest fragmentation places on them. Their increased exposure to humans and livestock leaves them vulnerable to cross-species transmission of emerging infectious diseases and pathogens. Therefore, their role as sentinels of ecosystems, …

Effects Of Acute And Chronic Nicotine Administration On Choice Of Probabilistic Outcomes, Katya A. Nolder

Graduate Theses, Dissertations, and Problem Reports (ETD)

Risky choice can be operationally defined as the choice for a larger, uncertain reinforcer over a smaller, certain reinforcer. Research suggests smokers engage in more risky or maladaptive decisions when compared to nonsmokers. The relation between nicotine and risky choice could benefit from further investigation, since nicotine is the active substance of tobacco products that maintains tobacco addiction. Acute nicotine administration has shown to alter risky choice; however, since the everyday smoker uses nicotine repeatedly, more research on chronic administration is warranted and would allow for assessment of tolerance or sensitization of these effects. The present study investigated effects of …

Formulation And Evaluation Of Fast Disintegrating Tablets Of Domperidone Using Chitosan-Glycine Conjugates As Superdisintegrant, Simran Kaur Zandu, Reena Kumari, Inderbir Singh

The Thai Journal of Pharmaceutical Sciences

Purpose: The present research was envisaged to employ chitosan-glycine conjugates as superdisintegrant for developing fast disintegrating tablets of domperidone. Materials and Methods: Chitosan-glycine conjugates were prepared by physical mixing and microwave-assisted technique. Micromeritic study, Fourier transform infrared, scanning electron microscopy, and X-ray diffraction methods were employed for characterizing the powdered conjugates. The formulated FDTs were evaluated for wetting time, water absorption ratio, disintegration time, in vitro drug release, and other tablet parametric tests. Results and Discussion: The effective pore radius of unadulterated chitosan was found to be 18.45±1.27 μm whereas the chitosan-glycine conjugates prepared by physical technique and microwave technique …

Development And Radiosynthesis Of A Novel Bifunctional Tri-Γ-Glutamic Acid Polypeptide For Gallium-68 Labeling, Wanchai Chongcharoen, Shuichi Shiratori

The Thai Journal of Pharmaceutical Sciences

Radiosynthesis of a novel bifunctional chelator for gallium-68 (Ga-68) chelation has been fabricated through peptide synthesis. Using of solid phase peptide synthesizer, linear structure of three repeating unit of glutamic acid was primarily generated. Protecting group of tert-butyl in intermediate was then cleaved and eventually yield as tri-γ-glutamic acid polypeptide (tri- γ-GAP). Mass spectrometry revealed m/z was 406.1378 that well corresponded with proposed structure of three repeating unit of glutamic acids. To label Ga-68 with synthesized tri-γ-GAP, the elution of 68GaCl3 was chelated to tri-γ-GAP with high temperature condition. It was subsequently purified through Sep-Pak C18 cartridge. Radio thin-layer chromatography …

Characterization Of Acyclovir-Isonicotinamide Cocrystal By Solvent Evaporation Method With Ethanol And Glacial Acetic Acid, Hansen Pradana Sutedjo, Agnes Nuniek Winantari, Roisah Nawatila

The Thai Journal of Pharmaceutical Sciences

Background: Acyclovir is used as the first-line therapy for genital herpes simplex virus, but acyclovir has low solubility and bioavailability. Acyclovir has a water solubility of 2.5 mg/ml at 37°C and belongs to Class IV according to the bioavailability classification system. Cocrystalization is a technology that can be used to improve the solubility of materials by modifying the physical properties of materials, such as melting points, stability, mechanical properties, and polymorphisms of materials. Materials and Method: This study aims to prepare cocrystal of acyclovir with isonicotinamide as coformer using different solvents, namely, ethanol and glacial acetic acid by solvent evaporation …

Doxepin Accelerates The Healing Process Of Burn Wounds In Mice, Elham Saberzadeh, Mohsen Zabihi, Ehsan Motaghi, Fatemeh Shishehbor

The Thai Journal of Pharmaceutical Sciences

Wound healing following a skin burn is still a concern due to poor effectiveness and the side effects of the available topical and systemic drugs. Doxepin hydrochloride is an approved antidepressant drug (Application No.: 022036) which is effective for the treatment of moderate pruritus in patients with eczema and atopic dermatitis. The current study has evaluated the effect of topical and systemic doxepin to improve the histopathologic process of second-degree burn wound in mice. The mice were divided into six groups (n = 6), including topical normal saline group, topical glycerin group, positive control group (topical phenytoin), topical doxepin 5% …

In Silico Approach For Hepatoprotective Activity Of Piper Crocatum Leaf Toward Cytochrome P450 2e1 Protein, I. Nyoman Ehrich Lister, Chrismis Novalinda Ginting, Ermi Girsang, Wahyu Widowati, Ika Adhani Sholihah

The Thai Journal of Pharmaceutical Sciences

Liver plays important roles in metabolism of harmful xenobiotics. Prolonged exposure to chemicals, daily dietary supplements, or pharmaceutical drugs may cause liver damage or hepatotoxicity. Acetaminophen is a well-known pharmaceutical drug causing hepatotoxicity through generation of reactive metabolite called N-acetyl-p-benzoquinone imine through Cytochrome P450 2E1 (CYP2E1) metabolism. In the present study, we intended to predict the possible hepatoprotective properties of red betel (Piper crocatum) leaves. Quantitative structure activity relationship (QSAR) was used to predict the antioxidant and anti-inflammatory potential of major compounds of red betel, namely, eugenol, isoeugenol, chavibetol, hydroxychavicol, and allylpyrocatechol. Molecular docking was performed to analyze binding mode …

Comparative Evaluation Of The Hepatoprotective Activity Of Methanol Leaf Extracts Of Pterocarpus Santalinoides Dc Obtained By Cold Maceration And Soxhlet Extraction Techniques, Thelma Ebele Ihedioha, Isaac Uzoma Asuzu, Aruh Ottah Anaga, John Ikechukwu Ihedioha

The Thai Journal of Pharmaceutical Sciences

Objectives: This study compared the hepatoprotective activity of Pterocarpus santalinoides cold maceration extract (PSCME) with P. santalinoides Soxhlet extract (PSSE). Materials and Methods: Phytochemical constituents of both extracts were determined. 45 albino rats, randomly assigned into 9 groups (1–9) of 5 rats each, were used for the study. Liver damage was induced in groups 1–8 using carbon tetrachloride (CCl4). Group 1 served as untreated control, Groups 2–7 were treated with 50, 250 or 500 mg/kg PSCME or PSSE, Group 8 was treated with 100 mg/kg silymarin, while Group 9 served as normal control. Treatment was done orally for 15 days. …

Teaching And Learning Of Smoking Cessation And Tobacco Control In The Pharmacy Program: A Cross-Sectional Survey Study, Pantira Parinyarux, Adinat Umnuaypornlert, Kornkaew Chanthapasa

The Thai Journal of Pharmaceutical Sciences

Introduction: Pharmacists play an important role in smoking cessation programs. A lack of knowledge among pharmacy students can create a barrier to providing smoking cessation support. Pharmacy training programs should integrate smoking cessation techniques into the core curriculum. Objective: We aimed to explore the current teaching practices for smoking cessation and tobacco control in pharmacy curricula in Thailand. Methods: A questionnaire surveying tobacco control curricula and teaching techniques were distributed to faculty members in all 19 pharmacy departments in Thailand. Results: Twenty-nine faculty members participated in this study. Most pharmacy programs start teaching smoking cessation and tobacco control in the …

Protein Phosphatase 2a In Metformin’S Action In Primary Human Skeletal Muscle Cells, Aktham H. Mestareehi

Wayne State University Dissertations

Diabetes is a group of metabolic diseases characterized by hyperglycemia caused by defects in insulin secretion, insulin action, or both. Diabetes is associated with damage, dysfunction, and failure of various organs, such as the eyes, heart, kid-neys, and brain. Diabetes is mainly classified into type 1 (T1DM) and type 2 diabetes (T2D). Diabetes affects more than 34 million people in the USA (about 1 in 10) and more than 90% of diabetic patients have type 2 diabetes (T2D). Insulin resistance is a main characteristic feature of type 2 diabetes. Skeletal muscle insulin resistance is con-sidered to be the primary defect …

Targeted Combination Therapy Of Triple-Negative Breast Cancer, Ketki Bhise

Wayne State University Dissertations

TARGETED COMBINATION THERAPY OF TRIPLE-NEGATIVE BREAST CANCERby KETKI BHISE May 2021 Advisor: Dr. Arun Iyer Major: Pharmaceutical Sciences Degree: Doctor of Philosophy Triple Negative Breast Cancer (TNBC) accounts for 10-20% of the total breast carcinoma cases. There is no FDA-approved targeted therapy for TNBC due to lack estrogen, progesterone and HER-2. We have identified the role of a hypoxia biomarker, carbonic anhydrase IX (CAIX) in proliferation and metastasis of TNBC. Based on this observation, we have developed CAIX-targeted Doxorubicin (Dox) prodrug, abbreviated as DoxAtz. To improve the delivery of DoxAtz to the tumor, we developed long circulating liposomes (LipoDoxAtz) and …

Therapeutic Dual-Targeting Of Cytosolic And Mitochondrial One-Carbon Metabolism, Aamod Sanjeev Dekhne

Wayne State University Dissertations

One-carbon metabolism (1CM) is compartmentalized in the mitochondria and cytosol and generates a host of metabolites critical to tumor propagation. Although drug-targeting of cytosolic 1CM remains a clinically-relevant mainstay, development of clinically-useful agents targeting mitochondrial 1CM remains elusive. Of particular pharmacological interest is the mitochondrial 1CM enzyme, serine hydroxymethyltransferase2 (SHMT2). SHMT2 expression correlates with the oncogenic phenotype in lung, colon, breast, glioma, and liver cancer and, overall, is the fifth-most differentially expressed metabolic enzyme in cancer cell versus normal tissue. Despite the unequivocal oncogenic importance and therapeutic potential of SHMT2, there are no clinically relevant (i.e. active in vivo) inhibitors …

Development And Characterization Of An Adaptable Aerosolized Methylene Diphenyl Diisocyanate Generation System, Simon Aubin, Loïc Wingert, Sébastien Gagné, Livain Breau, Jacques Lesage

Études primaires

Reactive semivolatile contaminants, such as isocyanates, can be particularly difficult to assess in occupational environments. While standard methods exist for isocyanates, there are still significant differences between the results they provide for various occupational environments or processes. This study presents the validation of a laboratory system for the generation of controlled atmospheres of isocyanates. A system consisting of different modules generated airborne methylene diphenyl diisocyanate (MDI) by nebulizing a solution into mixing and exposure chambers with control of flow rate, temperature, and relative humidity. Sampling was performed through an eight-port flow splitter that allowed only very slight within-test variability. MDI …

Occupational Exposure To Antineoplastic Drugs: What About Hospital Sanitation Personnel?, France Labrèche, Capucine Ouellet, Brigitte Roberge, Nicolas J Caron, Ahmed Yennek, Jean-François Bussières

Études primaires

Objective

Occupational exposure to antineoplastic drugs (ANPs) occurs mainly through dermal contact. Our study was set up to assess the potential exposure of hospital sanitation (HS) personnel, for whom almost no data are available, through contamination of surfaces they regularly touch.

Methods

In the oncology departments of two hospitals around Montreal, surface wipe samples of 120–2000 cm² were taken at 10 sites cleaned by the HS personnel and five other sites frequently touched by nursing and pharmacy personnel. A few hand wipe samples were collected to explore skin contamination. Wipes were analyzed by ultra-performance liquid chromatography tandem–mass spectrometry for …

The Protective Effects Of Mir-210 Modified Endothelial Progenitor Cells Released Exosomes In Hypoxia/Reoxygenation Injured Neurons, Sri Meghana Yerrapragada

Browse all Theses and Dissertations

Endothelial progenitor cells (EPCs) have been shown to provide beneficial effects on oxidative stress. Exosomes (EXs) released from these stem cells could be one of the major contributors, as they are known to convey the benefit of one cell to another cell via microRNAs (miRNA). At first, we determined that EPCs release more EXs when they are serum-starved for 48 hours., and by determining the microRNA-210 (miR-210) levels in the EXs, we found that miRNA is being transferred from cells to EXs. Meanwhile, miR-210 is gaining popularity in reducing elevated oxidative stress levels. In this study, we investigated the role …

The Effect Of Circadian Clock Modulation On Cisplatin Cytotoxicity, Nadeen Nibal Ahmad Anabtawi

Browse all Theses and Dissertations

Cisplatin is a DNA damage-based chemotherapeutic drug widely used to treat various types of cancers; however, the treatment's toxicity restricts its efficiency. Studies have shown that the circadian rhythm controls the DNA damage response and affects the repair pathways of cisplatin-induced DNA damage. Circadian clock modulation, therefore, has been proposed to be a potential mechanism for enhancing cisplatin tolerability. Here we used clock-enhancing molecules to evaluate the effect of pharmacological clock modulation on cisplatin cytotoxicity. Using cultured human cell lines, cisplatin cytotoxicity was found to be attenuated following treatment with circadian-enhancing molecules KS15 and SR8278. Moreover, the protein and mRNA …

Functions Of Atr Kinase In Terminally Differentiated Human Epidermal Keratinocyles And In Human Ex-Vivo Skin After Exposure To Ultraviolet B Radiation, Vivek Shashank Nag Gogusetti

Browse all Theses and Dissertations

The functions of Ataxia telangiectasia and Rad-3 related protein (ATR) is very much important in a cell, as it is a DNA damage response protein, which plays an important role in cell division, DNA repair and apoptosis. This protein helps in proliferation in the actively DNA dividing normal cells and in cancer cells. The functions of ATR in a proliferating cell are well studied and known to involve regulation of replication fork and cell cycle progression after DNA damage. Whereas, in a non-replicating cell, the functions of ATR are not so well known. In the human body, most of the …

Xeroderma Pigmentosum A Deficiency Results In Increased Generation Of Microvesicle Particles In Response To Ultraviolet B Radiation, Christian Lea Rajeshkumar

Browse all Theses and Dissertations

Xeroderma Pigmentosum is a genetic disorder in which ability to repair DNA damage such as from UV radiation is decreased. Nucleotide excision repair is known for repairing DNA damage caused by UV radiation and XPA plays a major role in recognizing and eliminating abnormal section of DNA. Therefore, XPA deficiency decreases repair efficiency of DNA. Of note, XPA deficiency is linked with photosensitivity. Microvesicle particles are membrane-bound particles which are released into the extracellular environment in response to multiple stimuli including the lipid Platelet activating factor (PAF). Previous studies have shown that XPA deficiency can induce increase production of reactive …

Stress-Induced Senescence In Human Dermal Fibroblasts : Effects Of Creatine And Nicotinamide Post Stress Treatment, Venkata Sravya Arikatla

Browse all Theses and Dissertations

In skin connective tissue, dermal fibroblasts appear to be the most prevalent cell type. They are in charge of making the extracellular matrix that makes up the skin's connective tissue, and also involved in wound healing. Moreover, they produce Insulin-like growth factor-1 (IGF-1) which helps in activation of Insulin growth factor-1 receptor (IGF-1R). This receptor helps to control cell proliferation and responses to DNA-damaging substances such as UVB radiation, reactive oxygen species (ROS), and therapeutic drugs. According to our findings, lack of IGF-1 expression in the dermis of elderly patients due to fibroblast senescence (senescence is characterized by which cells …

Survival, Growth, And Characterization Of Microbes In E-Liquids, Jessica Bunn

Master of Science in Forensic Science Directed Research Projects

Health risks associated with the use of e-cigarettes have become a concern in the last ten years, including the inhalation of volatile organic compounds, trace heavy metals, and cancer-causing agents. An additional, but poorly characterized health threat for e-liquids is the potential for bacterial contamination since the presence of pathogenic organisms can potentially cause disease from the inhalation of the microbes into the lungs. This work aims to investigate microbial growth and survival within the e-liquid matrix. Bacillus cereus T. strain and Escherichia coli were the chosen organisms for analysis of growth by absorbance, survival by viable plate counts, and …

Analysis Of Ethanol Aerosolized In An Electronic Cigarette By Headspace Gas Chromatography-Flame Ionization Detector (Gc-Fid) And Particle Size Separation, Erica R. Sales

Master of Science in Forensic Science Directed Research Projects

Electronic cigarettes (e-cigs) were designed as a healthier alternative nicotine delivery system, and involve the heating of e-liquids. These are composed of propylene glycol, vegetable glycerin, flavoring agents, and nicotine. Recently, ethanol has been identified as an unlabeled ingredient. The health consequences are currently unknown.

The purpose of this study is to quantify the amount of ethanol present in an aerosol cloud and to determine the size of the ethanol particles. A SubOx Mini-C e-cig was used. For ethanol quantification, the e-cig was attached to a Buchner Flask containing 150mL of deionized water, The system was attached to a vacuum …

Long Term Nutrient And Chlorophyll A Dynamics Across Long Island Sound And Impacts On Dissolved Oxygen Conditions Within The Western Sound (1991-2019), Sherry Perreira

Dissertations and Theses

Nitrogen overload, eutrophication, and hypoxia have been challenging and persistent water quality problems in Long Island Sound (LIS) over the past decades with major impacts on commercial industries, ecology, and recreational activities in the region. Recognizing these problems, the EPA enforced three phases of the Clean Water Act (CWA) to reduce nitrogen loads in an effort to improve this important estuary. This study examines how nitrogen (NH₃, NO_x & TDN), chlorophyll a (CHLA), and dissolved oxygen (DO) concentrations changed in LIS over the past 30 years, in response to water quality regulations as well as changes in …

Leakage Versus Material Filtration In Barrier Facemask Efficiency, Ali Bahloul, Clothilde Brochot, Barbara Layne

Études primaires

The World Health Association and many governmental agencies recommend the wearing of facemasks by the general public to prevent the spread of COVID-19. It is believed that masks can significantly protect others and may offer some protection to the wearer. Although there are standards for FFRs, surgical masks, and recently for barrier face coverings, they all indicate the level of protection for the wearer. However, testing facial masks not at the point of inhalation, but at the source, the exhale, offers a new perspective on how to impede particle emissions. In this paper, the experimental results show that, although the …

Synthesis, Molecular Docking, And Biological Evaluation Of Novel 2-(3-Chlorophenyl) Quinoline-4-Carboxamide Derivatives As Potent Anti-Breast Cancer And Antibacterial Agents, Kailas W. Shinde, Prashant S. Kharkar, Chetan P. Shah, Shrimant V. Rathod

The Thai Journal of Pharmaceutical Sciences

Objectives: The study aims to synthesize and to evaluate the anti-breast cancer and antibacterial activity of some novel quinoline-4-carboxamide derivatives. Materials and Methods: A series of novel quinoline analogs 6a-6j with varied substituent (X = H, F, OCH3, NO2) were synthesized from aniline through multi-step reactions in good yields. All analogues were confirmed by spectral characterization, namely, FT-IR, MS, 1H-NMR, and 13C-NMR. All the molecules were evaluated for their anticancer activity against a breast cancer cell line, MDA-MB-231 by MTT assay, and antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 6538p and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas …

Doxorubicin Modulates P-Glycoprotein Transcription Differently During Caco-2 Differentiation, Udomsak Udomnilobol, Suree Jianmongko

The Thai Journal of Pharmaceutical Sciences

P-glycoprotein (P-gp) is an efflux transporter protecting cells from various chemical threats. Upregulation of P-gp expression, mediated by reactive oxygen species (ROS), has been reported in doxorubicin-treated cells. However, during cell differentiation cellular redox status may vary. This study investigated the influence of cell differentiation on doxorubicin-mediated P-gp expression in Caco-2 cells, and its relation to cellular redox status. During 21-day culture, Caco-2 cells were divided into pre-, during-, and post-differentiation, based on total cell numbers, percentage of G0/G1 cells, and alkaline phosphatase activity. Our study demonstrated that Caco-2 cells were in a more reduced state on differentiation. At low …

Evaluation Of Acute Oral Toxicity Of Methanolic Fractions Of Sesbania Grandiflora Linn. Roots In Albino Mice, N. S. Vinay, S. Babitha, R. Nandeesh, S. Paramesh, E. Manjunath, J. P. Geetha, V. P. Veerapur, B. Swetha, H. V. Keerthi Prasanth

The Thai Journal of Pharmaceutical Sciences

Introduction: Although Sesbania grandiflora Linn. roots have valuable pharmacological effects, the comprehensive awareness about its toxicity potential has been lacking. Objectives: The objectives of the study were to assess the acute oral toxicity of methanolic fraction of S. grandiflora root (MFSGR). Materials and Methods: The female albino mice were divided into two groups (n = 5), one group served as normal control while the other treated with MFSGR (2000 mg/kg, p.o). Both the groups of mice were observed for 14 days for various parameters according to the Organization for Economic Cooperative and Development guidelines 425 TG. Results: Oral administration of …

Pharmacognostic And Chromatographic Evaluation Of Male And Female Flowers Of Coscinium Fenestratum For Berberine Content And Its Effect On Antioxidant Activity, T. S. Roopashree, Kuntal Das, N. Prashanth, K. Rakesh Kumar

The Thai Journal of Pharmaceutical Sciences

Coscinium fenestratum (CF) (Gaertn.) Colebr., [Family: Menispermaceae] is an endangered species of dioecious liana found in Western Ghats of India. The present investigation aimed with systematic analytical studies on the macroscopic, microscopic examination of male and female CF flowers, various solvent extractions, accompanied by phytochemical screening through chemical tests, identification of Berberine alkaloids, antioxidant activity, and Berberine quantification byhigh-performance thin-layer chromatography (HPTLC) process. Two different amounts of solvents (10 ml and 20 ml) with two different time intervals, that is, 15 min and 25 min, respectively, were used for extraction. Results revealed that both flowers had their own unique characters. …

Anthraquinones Extracted From Rubia Cordifolia Linn As Potential Ligands To Treat Alzheimer’S Disease, Pottella Srinivasulu, Janga Ramesh Babu, T.N.V. Ganesh Kumar, Padarthi Pavan Kumar, S. Vidyadhara

The Thai Journal of Pharmaceutical Sciences

Objective: The present investigation aims to predict the pharmacokinetic aspects and assessing the anti-Alzheimer’s activity using both molecular docking platform and ex vivo pharmacological studies on muscle contraction. Materials and Methods: 2-Methyl Anthraquinone (MAQ) and Quinizarine (QNZ) were isolated from Rubia cordifolia L., and evaluated for absorption, distribution, metabolism, excretion, and toxicity. Molecular docking was performed with the help of Mcule software on five drug targets acetylcholinesterase enzyme (AChE), cyclin-dependent kinase5 (CDK5), glycogen synthase kinase 3β (GSK3β), monoamine oxidase (MAO-B), and β-secretase enzyme (BACE). The pharmacological activity was screened by recording the muscle contractions of chick ileum. Results: The selected …

Current Perspectives On The Therapeutic Potential Of Mitragyna Speciosa And Its Derivatives On Animal Model, Norsyifa Harun, Illa Syafiqah Johari, Rima Atria Japarin, Farah Wahida Suhaimi, Zurina Hassan, Mohammed Shoaib

The Thai Journal of Pharmaceutical Sciences

The plant Mitragyna speciosa Korth. is receiving increased attention as a therapeutic substitution for opioid use disorder (OUD). The active alkaloids constituents of the plant, particularly mitragynine and 7-hydroxymitragynine, have been shown to modulate opioid receptors, acting as agonists at mu-opioid receptors. Given this pharmacology, several studies have examined the abuse and dependence potential of M. speciosa and its alkaloids in various animal models of dependence. In addition to action on opioid receptors, the Mitragyna alkaloids also appear to exert diverse activities at other receptors in the central nervous system which may explain the complex pharmacological profile of these alkaloids. …

Evidence For Intravenous Self-Administration Of Mitragynine In Fentanyl-Dependent Rats, Norsyifa Harun, Zurina Hassan, Surash Ramanathan, Mohammed Shoaib

The Thai Journal of Pharmaceutical Sciences

Introduction: Kratom (Mitragyna speciosa Korth) is currently used as an alternative for the self-treatment of pain and management of opioid dependence and withdrawal. Due to the opioid-like effect of the plant’s active alkaloid, mitragynine (MG), the evaluation of its ability to maintain self-administration in animal models of opioid dependence appears to be great significance. Objectives: Here, the ability of MG to cross-substitute to the reinforcing effects of the synthetic narcotic fentanyl is investigated. Methods: Rats with implanted catheters were allowed to self-administer fentanyl (2.0 μg/kg/infusion) on a fixed-ratio 1 of schedule of reinforcement. Results: A significant increase in lever pressing …