center for substance abuse research
Core Center of Excellence
“Center on intersystem regulation by drugs of abuse”
NIH/NIDA P30 DA13429
Program Director/Center PI: Unterwald
This Core Center of Excellence supports and enhances research related to drugs of abuse and addiction. Eight Core facilities are supported by this grant and serve as a resource to the general scientific community. The Cores are briefly described below. Please contact the Core Director for further information about the services provided.
Ellen M. Unterwald, PhD, Core Director
Lynn Kirby, PhD, Co-Investigator
The Animal Core serves as a centralized resource that provides mice with genetic deletions or mutations to the members of the Center, other research groups at the university, and the general scientific community. Genetically engineered mice are bred and maintained at the Central Animal Facility of Temple University, thus ensuring consistent background strains across studies, appropriate control mice, and ready access to mice of the age and sex necessary for experimentation. In-house breeding and use of the same animal strains by multiple investigators enhances collaborative studies and increases scientific synergy.
The Animal Core provides the following services:
- Breeding and maintenance of animals that have targeted gene deletions or express transgenes. Mouse lines currently being bred in the Animal Core include opioid receptor knockout mice (MOPR, KOPR, DOPR), cannabinoid receptor knockout mice (CB1, CB2, CB1/CB2), and chemokine receptor knockout mice (CCR5).
- Genotyping of the animals carried out in collaboration with the Molecular Core.
- Phenotyping of the animals characterized together with the Integrative Pharmacology Core.
|BIOCHEMICAL PHARMACOLOGY CORE
Lee-Yuan Liu-Chen, PhD,
The Biochemical Pharmacology Core provides the following services:
- Receptor binding: opioid receptors, dopamine receptors and nicotinic receptors. We will develop assays for others when necessary.
- Receptor autoradiography: opioid receptors. We will develop others when necessary.
- Assessment of receptor activation by determination of cAMP level, [35S]GTPÿS binding, and p44/42 MAP kinase phosphorylation
- Protein gel electrophoresis and immunoblotting
- Assessment of suitability of receptor antibodies for immunoblotting: opioid receptors initially. We will do others when needs arise.
Toby K. Eisenstein, PhD, Core Director
The Cell and Immunology Core provides the following services:
- Basic tests of immune function for mouse, human and rat cells including:
- Response of lymphocytes to mitogens
- Assay of Natural Killer (NK) cell activity
- Capacity for in vitro antibody formation
- Mixed Lymphocyte Reaction (MLR)
- Assays for levels of cytokines, chemokines, and neuropeptides using ELISA multiplex assays such as the Cytometric Bead Array assay
- Separate cells by magnetic bead separation
- Analyze expression of surface markers on cells using Flow Cytometry (FACS)
- Perform mycoplasma testing of cell lines
|DATABASE AND DRUG INTERACTION CORE
Ronald J. Tallarida, PhD, Core Director
There is a pressing need for a database that contains relevant quantitative information on combinations of drugs of abuse. Dr. Tallarida has studied and published extensively in the area of drug combinations. That effort, coupled with his numerous worldwide publications on drug combinations, is the basis of new component in this grant renewal application. Many drug combinations are well known for their approved use as well as their use on the street, (e.g., fentanyl + cocaine, heroin + methamphetamine, etc, and extensive combinations that involve alcohol or marijuana). This core is undertaking the development of a database derived from publications of laboratory-based studies and human use that include drug combinations of special relevance. By that we mean the legitimate medical use of a drug combination as well as common “street combinations”. The main objective is to search for and classify interactions as synergistic, sub-additive or simply additive. An additional specific aim is the inclusion of updated computational methodology—a computational and experimental design guide—that can be used by all researchers for assessing these interaction and distinguishing synergism and sub-additivity from simply additive interactions. This will be accomplished from a new website, accessible by all, from our Center on Substance Abuse Research.
|INTEGRATIVE PHARMACOLOGY CORE
Alan Cowan, PhD, Core Director
Ronald J. Tallarida, PhD, Co-Investigator
Martin W. Adler, PhD, Co-Investigator
Ellen B. Geller, Co-Investigator
The Integrative Pharmacology Core offers pharmacological testing services for the following endpoints in mice and/or rats:
- Irwin neurological screen of overt behavior
- Rotorod trials for motor coordination
- Automatic monitoring for ambulation and stereotypes
- Exploratory behavior in the Y-maze
- Assessment of anticonvulsant activity
- Analgesic/tolerance tests for acute, persistent and incisional pain
- Anti-inflammatory activity (carrageenan test)
- Antipruritic activity
- Physical dependence/withdrawal
- Body and brain temperature measurement
- Gastrointestinal transit
- Tests of anxiety- and depression-like behaviors
- Assessment of drug reward
Thomas J. Rogers, PhD, Core Director
This core facility provides a full range of molecular services to investigators with research interests which are relevant to drug abuse. The services provided include:
- Molecular cloning and expression vector design and construction
- Determination of sequences and restriction nuclease sites when necessary
- Analysis of gene expression using northern blot analysis, RNAse protection analysis, RT-PCR, and related techniques
- Analysis of gene promoter/enhancer function by reporter analysis
- Analysis of transcription factor activity by array screen, ChIP analysis, electrophoretic mobility shift analysis (EMSA), or nuclear run-on assays
- Creation of transcription/translation modulators including custom design of antisense oligonucleotides, interfering RNA design and construction, and the preparation of dominant-negative or inactive forms of gene products
- Genotyping services required for the Animal Core.are also carried out by the Molecular Core.
Center for Substance Abuse Research
Ellen B. Geller
3500 N. Broad Street
Medical Education and Research Bldg., 8th Floor
Philadelphia, PA 19140