A5050634480- Neurotransmitter Receptor Influence on Behavior
- Forensic Toxicology and Drug Analysis
- Genetic Associations and Epidemiology
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Neuroscience and Neuropharmacology Research
- Psychedelics and Drug Studies
- Pain Mechanisms and Treatments
- Smoking Behavior and Cessation
- Neuropeptides and Animal Physiology
- Crystallization and Solubility Studies
- Epigenetics and DNA Methylation
- X-ray Diffraction in Crystallography
- Cannabis and Cannabinoid Research
- Nicotinic Acetylcholine Receptors Study
- Alcohol Consumption and Health Effects
- Chemical synthesis and alkaloids
- Genetic Mapping and Diversity in Plants and Animals
- Veterinary Pharmacology and Anesthesia
- Obesity, Physical Activity, Diet
- Ion channel regulation and function
- Parkinson's Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Treatment of Major Depression
- Biochemical Analysis and Sensing Techniques
National Institute on Drug Abuse
2015-2025
National Institutes of Health
2015-2025
Office of Extramural Research
2023-2024
International Drug Development
2023
Universitat Autònoma de Barcelona
2023
Universitat de Barcelona
2023
Institut de Biomedicina de la Universitat de Barcelona
2023
United States Department of Health and Human Services
2005-2017
University College London
2012
London School of Hygiene & Tropical Medicine
2012
Abstract Identification of N,N-dimethylpentylone (DMP) in counterfeit “Ecstasy” and “Molly” tablets poses risk to public health due its adverse effects. Little information is available regarding the pharmacological activity or relevant blood tissue concentrations DMP, even less known about other structurally related beta-keto methylenedioxyamphetamine analogs on recreational drug markets, such as N-propyl butylone. Here, a novel toxicological assay utilizing liquid chromatography–tandem...
<h3>Context</h3> Smoking remains a major public health problem. Twin studies indicate that the ability to quit smoking is substantially heritable, with genetics overlap modestly of vulnerability dependence on addictive substances. <h3>Objectives</h3> To identify replicated genes facilitate smokers' abilities achieve and sustain abstinence from (hereinafter referred as quit-success genes) found in more than 2 genome-wide association (GWA) successful vs unsuccessful abstainers, and,...
Abstract Potential roles for variants in the human BDNF gene brain disorders are supported by findings that include: (a) influences this trophic factor can exert on important neurons, regions, and neurotransmitter systems, (b) changes expression follow altered neuronal activity drug treatments, (c) linkages or associations between genetic markers near traits include depression, schizophrenia, addictions, Parkinson's disease. We now report assembly of more than 70 kb genomic sequence,...
Addictions are substantially heritable complex disorders. We now report whole genome association studies that identify 89 genes likely to contain variants contribute addiction vulnerability, using previously- and newly-validated microarray based pooling assays. Each gene contains clustered single nucleotide polymorphisms (SNPs) display significant allele frequency differences between abusers controls in each of the two samples studied with 639,401 SNP arrays confirmatory SNPs from other...
Classical genetic studies indicate that nicotine dependence is a substantially heritable complex disorder. Genetic vulnerabilities to largely overlap with on other addictive substances. Successful abstinence from displays substantial components as well. Some of the heritability for ability quit smoking appears genetics and some does not. We now report genome wide association dependent individuals who were successful in abstaining cigarette smoking, not ethnically-matched control subjects...
Dopamine transporter messenger RNA (mRNA) expression was assessed by in situ hybridization over individual pigmented neurons from the substantia nigra pars compacta midbrain sections 7 parkinsonian and age-matched, neurologically normal patients. In control brains, high levels of dopamine mRNA were noted compacta; adjacent nucleus paranigralis ventral tegmental area displayed less hybridization. Nigra surviving brains patients with Parkinson's disease only 57% intensity nigral brains. The...
Association genome scanning can identify markers for the allelic variants that contribute to vulnerability complex disorders, including alcohol dependence. To improve power and feasibility of this approach, we report validation "100k" microarray-based frequency assessments in pooled DNA samples. We then use approach with unrelated alcohol-dependent versus control individuals sampled from pedigrees collected by Collaborative Study on Genetics Alcoholism (COGA). Allele differences between are...
Oligonucleotides and a full-length cDNA encoding functional dopamine transporter (DAT1) hybridize to 3.7 kb mRNA that is concentrated in prepared from midbrain absent specimens cerebellum or cerebral cortex. In situ hybridization reveals substantial densities overlying neurons of the substantia nigra, pars compacta, parabrachialis pigmentosus region ventral tegmental area (VTA). Neurons linear paranigral VTA regions display lower levels expression. Preliminary studies arcuate suggest modest...
Context:We can improve understanding of human methamphetamine dependence, and possibly our abilities to prevent treat this devastating disorder, by identifying genes whose allelic variants predispose dependence.Objective: To find "methamphetamine dependence" identified each 2 genome-wide association (GWA) studies independent samples methamphetamine-dependent individuals matched controls.Design: Replicated GWA results in casecontrol studies.Setting: Japan Taiwan.Participants: Individuals with...
Neurexins are cell adhesion molecules that help to specify and stabilize synapses provide receptors for neuroligins, neurexophilins, dystroglycans α-latrotoxins. We previously reported significant allele frequency differences single nucleotide polymorphisms (SNPs) in the neurexin 3 (NRXN3) gene each of two comparisons between individuals who were dependent on illegal substances controls. now report work clarifying details NRXN3's structure variants documenting association NRXN3 SNPs with...
Epigenetic consequences of exposure to psychostimulants are substantial but the relationship these changes compulsive drug taking and abstinence is not clear. Here, we used a paradigm that helped segregate rats reduce or stop their methamphetamine (METH) intake (nonaddicted) from those continue take compulsively (addicted) in presence footshocks. We model investigate potential alterations global DNA hydroxymethylation nucleus accumbens (NAc) because neuroplastic NAc may participate...
Association genome scanning is of increasing interest for identifying the chromosomal regions that contain gene variants contribute to vulnerability complex disorders, including addictions. To improve power and feasibility this approach, we have validated “10k” microarray-based allelic frequency assessments in pooled DNA samples used approach seek differences between heavy polysubstance abusers well characterized control individuals. Thirty-eight loci SNPs display robust allele controls both...
Abstract Synthetic cathinones continue to proliferate in clandestine drug markets worldwide. N ‐ethylnorpentylone (also known as ‐ethylpentylone or ephylone) is a popular emergent cathinone, yet little information available about its toxicology and pharmacology. Here we characterize the analytical quantification, clinical presentation, pharmacological mechanism of action for ‐ethylnorpentylone. Liquid chromatography coupled tandem mass spectrometry (LC–MS/MS) was used quantify blood obtained...
Ibogaine is the main psychoactive alkaloid produced by iboga tree (Tabernanthe iboga) that has a unique therapeutic potential across multiple indications, including opioid dependence, substance use disorders, depression, anxiety, posttraumatic stress disorder (PTSD), and traumatic brain injury (TBI). We systematically examined effects of ibogaine, its metabolite noribogaine, series analogs at monoamine neurotransmitter transporters, some which have been linked to oneiric these substances....