M. Imad Damaj, Ph.D.
- University of Paris XI, 1991
- Drugs of abuse
- Molecular neuroscience
- Behavioral pharmacology
- Mouse genetics
- Drug development
Our goal is to understand molecular and pharmacological neurobiological mechanisms in behaviors related to addiction and dependence. We use genetic and pharmacological approaches to integrate the biochemical, molecular and anatomical levels of investigation in understanding addictive behavior.
A primary focus of our laboratory is the role of neuronal nicotinic acetylcholine receptors in brain function, addiction and development, with a focus on behaviors related to nicotine addiction and smoking in both adult and adolescence. We are also interested in signaling molecules downstream of nicotinic receptors, such as CREB, CaM kinase II and IV and phosphatases that may mediate long-term changes in behavior following exposure to nicotine and other drugs of abuse.
The role of other neuronal systems in nicotine dependence is an important aspect of our research focus. We are studying the role of the neuronal cannabinoid system in the development of nicotine addiction. In collaboration with the Lichtman’s group at VCU, we are using genetically modified mice and selective pharmacological ligands for the endocannbinoid system to study nicotine dependence and pharmacology.
We recently initiated with the groups of Kenneth Kendler, M.D., Department of Psychiatry; Xiangning Chen, Ph.D., Department of Psychiatry; and Michael Miles, M.D., Ph.D., Department of Pharmacology and Toxicology at VCU important collaborative studies using genetic mapping and functional genomics to understand the molecular mechanisms approaches involved in nicotine exposure in selected inbred mouse strains.
These basic and preclinical approaches are providing our group with new targets and potential pharmacotherapies for nicotine dependence. For this aspect of drug development, we work with both F. Ivy Carroll, Ph.D., of Research Triangle Park in North Carolina and Ron Lukas, Ph.D., of Barrow Neurological Institute in Phoenix as part of The National Cooperative Drug Discovery Group, which collaborates with the National Institutes of Health to discover novel treatments for tobacco smoking cessation.
Finally, our work continues on the role of nicotinic receptors in psychostimulants and alcohol addiction as well as chronic pain and inflammation. We believe that integrating molecular and systems levels will be necessary to understand the neurobiological basis for addictive behaviors. Our laboratory is funded by several National Institute of Health grants and contracts.
Carroll FI, Muresan AZ, Blough BE, Navarro HA, Mascarella SW, Eaton JB, Huang X, Damaj MI and Lukas RJ. (2011) Synthesis of 2-(Substituted Phenyl)-3,5,5-trimethylmorpholine analogues and their effects on monoamine uptake, nicotinic acetylcholine receptor function and behavioral effects of nicotine. Journal of Medicinal Chemistry.
Carroll FI, Blough BE, Mascarella SW, Navarro HA, Eaton JB, Lukas RJ and Damaj MI. (2010) Nicotinic acetylcholine receptor efficacy and pharmacological properties of 3-(substituted phenyl)-2β-substituted tropanes. Journal of Medicinal Chemistry.
George O, Lloyd A, Carroll FI, Damaj MI and Koob GF. (2011) Varenicline blocks nicotine intake in rats with extended access to nicotine self-administration. Psychopharmacology (Berl). 213(4):715-22.
Zhang Y, Gilliam A, Maitra R, Damaj MI, Tajuba JM, Seltzman HH and Thomas BF. (2010) Synthesis and biological evaluation of bivalent ligands for the cannabinoid 1 receptor. Journal of Medicinal Chemistry. 53(19):7048-60.
Abdrakhmanova GR, Blough BE, Nesloney C, Navarro HA, Damaj MI and Carroll FI. (2010) In vitro and in vivo characterization of a novel negative allosteric modulator of neuronal nAChRs. Neuropharmacology. 59(6):511-7.
Abdrakhmanova GR, AlSharari S, Kang M, Damaj MI and Akbarali HI. (2010) α7-nAChR-mediated suppression of hyperexcitability of colonic dorsal root ganglia neurons in experimental colitis. American Journal of Physiology – Gastrointestinal Liver Physiology. 299(3):G761-8.
Damaj MI, Grabus SD, Navarro HA, Vann RE, Warner JA, King LS, Wiley JL, Blough BE, Lukas RJ and Carroll FI. (2010) Effects of hydroxymetabolites of bupropion on nicotine dependence behavior in mice. Journal of Pharmacology and Experimental Therapeutics. 334(3):1087-95.
Lukas RJ, Muresan AZ, Damaj MI, Blough BE, Huang X, Navarro HA, Mascarella SW, Eaton JB, Marxer-Miller SK and Carroll FI. (2010) Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation. Journal of Medicinal Chemistry. 53(12):4731-48.
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA and Damaj MI. (2010) Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. Journal of Pharmacology and Experimental Therapeutics. 334(1):137-46.
Jackson KJ, Carroll FI, Negus SS and Damaj MI. (2010) Effect of the selective kappa-opioid receptor antagonist JDTic on nicotine antinociception, reward and withdrawal in the mouse. Psychopharmacology (Berl). 210(2):285-94
Carroll FI, Blough BE, Mascarella SW, Navarro HA, Eaton JB, Lukas RJ and Damaj MI. (2010) Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for smoking cessation. Journal of Medicinal Chemistry. 53(5):2204-14.
Carroll FI, Ma W, Deng L, Navarro HA, Damaj MI and Martin BR. (2010) Synthesis, nicotinic acetylcholine receptor binding and antinociceptive properties of 3′-(substituted phenyl) epibatidine analogues. Nicotinic partial agonists. Journal of Natural Products. 73(3):306-12.