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Division of Basic Neuroscience and Behavioral Research (DBNBR)

Description:

DBNBR’s basic neuroscience and behavioral research focuses on understanding the mechanisms, characteristics, and processes of drug abuse both in adult and developing organisms. Basic behavioral, cognitive, neurobiological, cellular, molecular, chemical, and genetics research aims at characterizing and understanding drug seeking, compulsive behavior, and addictive processes. These research areas necessarily include studies of normal processes. Using both animal and human studies, basic behavioral research focuses on behavioral and cognitive processes that may or do lead to drug initiation, and the behavioral and cognitive consequences of drug abuse. Neurobiology research focuses on the neural mechanisms and substrates underlying behavioral and cognitive processes and vulnerability factors associated with drug abuse, addiction, sensitization, tolerance, and relapse. DBNBR also supports basic chemistry and pharmacological studies focusing on structure/activity relationships, definition, and characterization of systems involved in drug actions, chemical synthesis of new ligands, pharmacokinetics, analytical methods, understanding basic mechanisms of drug action and drug testing. The focus of maternal and paternal drug use is to ascertain the consequences of drug exposure on brain development as well as on other physiological systems.

Computational and theoretical modeling of biological systems and behavioral processes, biomedical computing and/or information science and technology development is supported by DBNBR.

1. Metabolomics in Drug Abuse Research. Metabolomics is the study of all molecules of a cell or organism and their identification and quantification that helps to understand the cellular regulation, metabolic pathways and activity and response under normal and other conditions. This technique thus could be used to develop metabolic profiling of normal or healthy subjects and subjects under the influence of substances of abuse or those undergoing drug rehabilitation programs.

NIDA is looking for applications on development of novel metabolomics technologies toward practical application in pathway and network investigation in biological systems particularly in understanding the mechanisms of drug addiction and discovering biomarkers for developing treatment for drug addiction.

Phase I application should demonstrate the feasibility of developing new metabolomics technology and phase II should focus on the application of this technology in drug abuse research.

Hari H. Singh, Ph.D.

301-443-1887

E-mail: hs87j@nih.gov

2. Development of Alternate Drug Delivery Dosage Forms for Drugs Abuse Studies. SBIR applications are solicited to design and develop alternate dosage forms for drugs that are not orally administered such as nicotine, marijuana, heroin, etc. Phase I should demonstrate the feasibility of the proposed innovation and Phase II, the development and testing of the innovation.

Hari H. Singh, Ph.D.

301-443-1887

E-mail: hs87j@nih.gov

3. Discovery of New Chemical Probes. SBIR applications are solicited to discover new chemical compounds as biological probes either by synthesis or isolation from natural resources in studying the mechanisms of action of drugs of abuse. Such substances could be new chemical compounds, drug products, or peptides. Currently there are several ligands available through the NIDA drug supply system such as SR 141716A, SR144528, CP 55,840, anandamide, epibatidine, Kaffiralin 1 and 2, etc. All probes for cannabinoids, neuropeptides, nicotinic acetylcholinergic receptors and related probes for drug abuse study are encouraged. In addition applications on biological screening of such new compounds as potential ligands for drug abuse research will also be considered.

Phase I should demonstrate the feasibility of the proposed innovation and Phase II, the development, characterization, testing, and screening of innovation. It should also be demonstrated that the new or modified chemical compounds are suitable for drug abuse research.

Rao S. Rapaka, Ph.D.

301-443-1887

Email: rr82u@nih.gov

4. Discovery and Study of Psychoactive Components of Botanicals. NIDA is looking for applications to develop methods for the isolation, purification, identification and characterization of active and inactive ingredients of herbal plants (stimulants, hallucinogenic, analgesics, and/or narcotics) and evaluation of their biological properties. Such studies may include chemistry, toxicology, pharmacodynamics, pharmacokinetics and the mechanisms of action of active and inactive ingredients to understand their efficacy, usefulness, adverse effects and abuse potential.

Phase I should demonstrate the feasibility of the proposed innovation and Phase II, the development, characterization, testing, and screening of innovation.

Rao S. Rapaka, Ph.D.

301-443-1887

Email: rr82u@nih.gov

5. Virtual Reality for Treatment of Pain. Virtual Reality (VR) exposure can reduce reported pain during wound care. Grant applications are sought to examine the utility of VR technologies in the treatment of various types of pain. Development of treatments for both acute and chronic pain is sought. These treatments can be based in clinical settings or the patients’ homes. Phase I testing should establish the feasibility of the use of this technology in the particular population to be tested. Phase I should also produce data that demonstrates that this methodology is effective for the particular type of pain being treated. Phase II should involve larger-scale testing (e.g., more subjects and treatment trials) examining various treatment parameters (e.g., timing of treatment, types of VR environments). The focus of Phase II testing should be the refinement of this treatment for use in pain patients.

David Thomas, Ph.D.

301-435-1313

Email: dt78k@nih.gov

6. Virtual Reality for the Treatment of Drug Abuse. Virtual Reality (VR) can be a useful clinical tool. In this particular study, VR exposure was used to allow patients to selectively not attend to an otherwise painful procedure. Drug abuse, like pain, is a problem that is strongly impacted by stimuli in the abuser’s environment and psychological factors. Thus, it is reasonable to assume that VR may be useful in allowing individuals to ignore drugs cravings, withdrawal symptoms or environmental cues that promote drug abuse. Grant applications are sought to examine the utility of VR technologies in the treatment of various types of drug abuse. These treatments can be based in clinical settings or the patients' homes. These treatments can be developed to address drug withdrawal, drug craving or on-going drug related behaviors. The development of VR technologies to address abuse of all types of drugs (e.g., cocaine, marijuana, nicotine, alcohol, inhalants) is sought. Phase I testing should establish the feasibility of the use of this technology for the particular drug problem addressed (e.g., cocaine craving, opioid withdrawal) and should also produce data that demonstrates that this methodology is effective for the particular drug problem. Phase II should involve larger-scale testing (e.g., more subjects and treatment trials) examining various treatment parameters (e.g., timing of treatment, types of VR environments). The focus of Phase II testing should be the refinement of this treatment for use in the treatment of drug abusers.

David Thomas, Ph.D.

301-435-1313

Email: dt78k@nih.gov

7. Development of a Virtual Reality Environment for Teaching about the Impact of Drug Abuse on the Brain. Virtual reality (VR) is emerging as a technology with a multitude of uses within the medical sciences. In terms of the science of drug abuse, it is being developed as a treatment tool. The current solicitation seeks the development of a virtual reality environment that can be used in educational settings to teach about how drugs of abuse (both illicit and licit) affect the brain and behavior.

The cost of portable hardware needed to present a VR environment is relatively inexpensive. If education programs like the one sought in this solicitation were available, it is likely that VR would be used as a teaching tool in many settings, including classrooms and museums.

The particular program sought here is to present an interactive three-dimensional virtual brain that shows normal brain functions and, in contrast, brain function after exposure to drugs of abuse. This technology could illustrate the neurotoxic and long-term effects of drug abuse on the brain. This VR may include other features that are not described above, provided that it will be useful in educating individuals about the medical, behavioral and social effects of drug abuse.

The phase I application should develop a beta version of the program. Further, the phase I application should include a preliminary demonstration of “usability,” where it is shown that the types of people being educated with this program (e.g. teachers) can effectively operate this system without extensive training. Further, it should be demonstrated that the hardware is easily worn by subjects, and that the subjects can rapidly understand how to effectively interact in the VR environment.

David Thomas, Ph.D.

301-435-1313

Email: dt78k@nih.gov

8. Nanoscience-based Design of Therapies for Substance Abuse Treatment. Nanoscience and nanotechnology, by manipulating matter at the atomic or molecular levels, are emerging research areas that have the potential to fundamentally transform the study of biological systems and lead to the development of new methods for detection, prevention, and treatment of substance abuse and related disease states. NIDA invites nanotechnology-based applications in the following areas:

a. Methods to enhance the efficacy of FDA-approved compounds by reducing their size to the nanoscale range to alter absorption, distribution, metabolism, or excretion.

b. Development of new compounds, through manipulation of matter at the atomic or molecular levels that could more readily pass the blood-brain-barrier or cell membranes.

c. Development of nanoscale particles for controlled targeted delivery of therapeutics, genes, or antibodies.

d. Methods to enhance existing imaging technologies using magnetic properties at the nanoscale.

e. Application of nanostructures (e.g. noble metal nanoparticles, quantum dots, and nanolithographic structures that show promise for diagnostic development) for identification and analysis of genes, proteins, and other biological molecules implicated in the actions of drugs of abuse.

Applications are invited from any of the above areas. Phase I should demonstrate convincingly the viability of the proposed innovation, whereas Phase II should carry out the development, characterization, testing, and screening of the innovation.

Thomas G. Aigner, Ph.D.

301-435-1314

Email: ta17r@nih.gov

9. Functional Genomics Resources and Strategies. In the post-genomic era, an explosion of gene discovery studies utilizing strategies such as genome-wide association scans, microarrays, and proteomics have identified a host of genes/gene variants associated with susceptibility to, or protection from, diseases of addiction. A critical next step is to validate these candidate genes/variants to determine which ones play an authentic functional role in mediating addiction. Functional validation could occur at many different phenotypic levels ranging from the molecular to the behavioral. Studies could investigate a few high priority genes/variants or could test several hundred genes/variants rapidly. The development of resources and strategies that would facilitate functional validation of genes/gene variants include (but are not limited to) the following areas:

a. Gene/variant effects on subcellular localization, stability, or function of mRNAs/proteins relevant to drug addiction.

b. The development of imaging and other strategies to identify gene/variant effects on neuronal or brain functions relevant to addiction.

c. Strategies to identify gene/variant effects on behavior, such as response to addictive stimuli, stress, or changes in social situations.

d. RNA interference-mediated depletion of candidate genes in cells or whole organisms to look for phenotypic alterations such as changes in synapse, dendritic spine, or cell morphology, gene expression, or behavioral responses to drugs of abuse.

e. Strategies exploiting the growing collection of genetic mutants in candidate genes (particularly utilizing model organisms such as mouse, zebrafish, Drosophila, C. elegans or yeast) to functionally validate genes/variants.

f. Approaches enabling comparison of wild type protein function to the function of allelic variants using in vivo transgenes or in vitro biochemical assays, especially if these approaches reveal whether a variation increases or decreases gene function.

g. Systems-based approaches investigating whether a set of candidate genes is co-expressed in a particular brain region or cell type, physically interacts with one another, or functions together in a signal transduction cascade are also of great interest.

h. Approaches to ascribe drug abuse-related function to genes/variants in non-coding RNAs, microRNAs, gene regulatory elements, gene copy number, or other putative non-protein coding regions of the genome.

i. Methods of translating functional studies in model systems to validate gene/variant function in humans.

John Satterlee, Ph. D.

(301)-435-1020

Email: satterleej@nida.nih.gov

10. Genetic Studies. The National Institute on Drug Abuse is interested in applications that would facilitate the identification of genetic loci that confer vulnerability to substance abuse and addiction. Areas of interest include but are not limited to:

a. Collection and genotyping of human pedigrees and sib-pairs for vulnerability or resistance to drug abuse.

b. Isolation and identification of mutant strains in genetic model systems such as Zebra fish, Drosophila, C. elegans, mice, and rats that are more vulnerable or resistant to drugs of abuse.

c. Throughput screens for identifying genetic vulnerability to addiction in genetic model systems.

d. Development of transgenic models for drug abuse using bacterial artificial or yeast artificial chromosomes.

e. Development of software and databases for candidate genes for drug abuse.

f. Identification and mapping of functional polymorphisms of candidate genes for drug abuse.

g. Placement of candidate genes for drug abuse on biochips.

h. Marker-assisted breeding of congenic mouse and rat strains for mapping quantitative trait loci associated with addiction and drug abuse.

i. Vectors for gene transfer into neurons.

Jonathan Pollock, Ph.D.

301-443-1887

Email: jp183r@nih.gov

11. Effects of Drugs at the Cellular Level . Development of new imaging techniques, reagents and related hardware and software for dynamic investigations of the effects of drugs of abuse on cellular activities and communications. For example, these techniques might include, but are not limited to, development and utilization of reagents for magnetic resonance microscopy and other MRI methods; development of methodologies applying functional MRI to drug abuse studies; the use of dyes, intrinsic signals, and other optical indicators for studying signal transduction mechanisms, the regulatory control of protein entities (such as phosphorylation), and neuronal excitatory and inhibitory pathways. Areas of interest may include but are not limited to:

a. Studies using molecular biological techniques to scale-up protein production for investigations aimed at enhancing understanding of the structure, function and regulation of molecular entities involved in the cellular mechanisms through which abused drugs act.

b. Validated in vitro test systems can reduce the use of animals in screening new compounds that may be of potential benefit in treating drug abuse. Test systems are needed to evaluate activity at receptors or other sites of action, explore mechanism(s) of action, and assess potential toxicity.

c. With the recent success in molecular cloning of various drug abuse relevant receptors, enzymes, and other proteins, researchers will elucidate the molecular mechanism of action of these drugs. Studies to generate strains of transgenic animals carrying a gene of interest are solicited. Of special interest are knockout and tissue-specific knockout animals. These animals can be used to identify gene function, and to study the pharmacological, physiological, and behavioral role of a single gene.

Jonathan Pollock, Ph.D.

301-443-1887

Email: jp183r@nih.gov

12. Research Resources. The National Institute on Drug Abuse is interested in applications that would generate the following resources for drug abuse research:

a. Resources for the application of genetic engineering to dynamically monitor neuronal function.

b. C57BL6 Mouse embryonic stem cells and spermatogonial stem cells.

c. Turnkey technology for proteomics such as the development of protein and peptide chips to study drug effects on neuronal mechanisms.

d. Antibodies, aptamers, ligands, etc. relevant to drug abuse research.

Jonathan Pollock, Ph.D.

301-443-1887

Email: jp183r@nih.gov

13. Computation, Modeling and Data Integration in Drug Abuse Research.

a. Development of software or other tools, which enable data integration, and the development of computational models related to addiction and other medical consequences of substance abuse, e.g. tools that enable the integration of proteomics, genomics, transcriptomics, metabolomics and other data into applications leading to systems understanding of drug effects upon biological systems, or developing innovative approaches for managing knowledge and integrating information from text, data, image, and other sources or files generated in addiction research.

b. Tools, which enable multilevel and multiscale modeling of biological and behavioral systems relevant to substance abuse research, such as those relevant to evaluations of expected utility.

c. Development of software tools and interactive technologies (such as applications of grid technologies and networked appliances) which enable the prevention, treatment and study of substance abuse as well as the evaluation of prevention and treatment strategies.

Karen Skinner, Ph.D.

301-435-0886

Email: Ks79x@nih.gov

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