We propose to use the power and ease of C. elegans genetics in a core capacity to extend existing substance abuse research in new directions. We will use this genetically-tractable organism to pursue novel areas of study related to funded projects and to answer other questions not easily addressed in a mammalian system that are posed by ourselves and the large group of drug abuse researchers at this and neighboring institutions. The end goal of this core-provided research will be to better understand mechanisms of action of drugs of abuse, including identification and elaboration of genes and pathways that are important in drug effects, and to provide a biological system where alterations in nervous system function can be genetically controlled with ease to aid in drug development and drug selection. This core will allow investigators who would not otherwise make use of C. elegans in their own laboratories the opportunity to collaborate with scholars who have extensive experience with this organism and together pursue these novel lines of research investigation. There are three main areas of focus proposed by this C. elegans genetics core. 1) To use C. elegans genetics, pharmacology and a battery of phenotypic assays to understand the effects of alterations in specific genes, specific biological pathways or to better understand the effect of a drug with unclear mechanisms of action. This approach will link the action of drugs with well characterized biological pathways and neurotransmitter systems that can be dissected further using C. elegans genetics. 2) To use C. elegans to carry out reverse and forward genetic screens for genes that are important in mediating phenotypic effects of interest, such as drug-induced phenotypes, or phenotypes produced through alteration of a biological system related to substance abuse. This approach has the potential to identify genes not previously known to be involved with specific drug effects. 3) To use C. elegans to develop living bioassays to take advantage of whole organism drug effects and integration of to vivo biological systems. This approach will allow for refinement of drug development strategies using a whole animal system. These approaches will bring the innovation associated with this powerful genetic system to substance abuse research and generate significant novel findings that will allow researchers to better understand the genetic underpinnings of the mechanisms of action of drugs of abuse.

Public Health Relevance

C. elegans is a powerful genetic model system with a relatively simple nervous system that shares many conserved components with the human brain. Genetic approaches utilizing mutants and transgene techniques will be used to identify genes and biological processes that are important for the action of drugs of abuse and to allow for the development of drugs used to treat substance abuse.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Center Core Grants (P30)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1-EXL-T (02))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Virginia Commonwealth University
United States
Zip Code
Poklis, Justin L; Mohs, Amanda J; Wolf, Carl E et al. (2016) Identification of Drugs in Parenteral Pharmaceutical Preparations from a Quality Assurance and a Diversion Program by Direct Analysis in Real-Time AccuTOFTM-Mass Spectrometry (DART-MS). J Anal Toxicol 40:608-616
Poklis, Justin; Poklis, Alphonse; Wolf, Carl et al. (2016) Two Fatal Intoxications Involving Butyryl Fentanyl. J Anal Toxicol 40:703-708
Banks, Matthew L; Smith, Douglas A; Kisor, David F et al. (2016) Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys. Pharmacol Biochem Behav 141:58-65
Grim, T W; Morales, A J; Gonek, M M et al. (2016) Stratification of Cannabinoid 1 Receptor (CB1R) Agonist Efficacy: Manipulation of CB1R Density through Use of Transgenic Mice Reveals Congruence between In Vivo and In Vitro Assays. J Pharmacol Exp Ther 359:329-339
Wolf, Carl E; Poklis, Justin L; Cumpston, Kirk et al. (2016) Acute dilated cardiomyopathy and myocardial injury after combined 4-fluoroamphetamine and modafinil ingestion. Drug Test Anal :
Hutsell, Blake A; Baumann, Michael H; Partilla, John S et al. (2016) Abuse-related neurochemical and behavioral effects of cathinone and 4-methylcathinone stereoisomers in rats. Eur Neuropsychopharmacol 26:288-97
Mukhopadhyay, Partha; Baggelaar, Marc; Erdelyi, Katalin et al. (2016) The novel, orally available and peripherally restricted selective cannabinoid CB2 receptor agonist LEI-101 prevents cisplatin-induced nephrotoxicity. Br J Pharmacol 173:446-58
Xu, Changqing; Hermes, Douglas J; Mackie, Ken et al. (2016) Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices. J Neuroimmune Pharmacol 11:316-31
Alajaji, Mai; Lazenka, Matthew F; Kota, Dena et al. (2016) Early adolescent nicotine exposure affects later-life cocaine reward in mice. Neuropharmacology 105:308-17
Grim, Travis W; Samano, Kimberly L; Ignatowska-Jankowska, Bogna et al. (2016) Pharmacological characterization of repeated administration of the first generation abused synthetic cannabinoid CP47,497. J Basic Clin Physiol Pharmacol 27:217-28

Showing the most recent 10 out of 63 publications