Faculty Directory

David Perry

David Perry

Adjunct Professor of Pharmacology & Physiology

Office Phone: 202-994-3541
Email:
Department: Pharmacology & Physiology

Education

  • BA, Harvard University, 1970
  • PhD, University of California, San Francisco, 1981

Teaching

Course director: MMED8280 - Neuropharmacology & Neurophysiology
Co-course director: MMED 8214 - Biomedical Seminars
Lecturer: BMSC8210; HSCI116; PHAR170; PHAR6201; PHAR6202; PHAR 6207; PHAR6208; PHYS6201; PHYS6211; PHYS 6212

Director, Pharmacology and Neuroscience concentrations in Molecular Medicine PhD Program, GW Institute for Biomedical Sciences

Research

The research focus in my lab is the neurobiology of nicotine. Nicotine addiction is the driving force behind the continued widespread use of tobacco products, which is the largest preventable cause of disease in the United States. We use rat models to study the effects of chronic nicotine exposure on neurotransmitter systems and gene expression in the CNS. We have pioneered the use of receptor autoradiography, using a combination of selective radioligands and competitors, to map the distribution of subtypes of nicotinic receptors (nAChRs) in rat brain. Using quantitative autoradiography, we demonstrated that chronic exposure to nicotine causes up-regulation of one the major subtypes, alpha4beta2, and to a lesser extent alpha7, while causing no change in the alpha3beta4 subtype, and actually down-regulating alpha6beta2 receptors. Using quantitative immunoprecipitation techniques in collaboration with Dr. Ken Kellar of Georgetown, we found that co-expression of the alpha5 subunit with alpha4beta2 inhibits nicotine-induced up-regulation, and likewise that co-expression of the beta3 subunit with alpha6beta2 inhibits its down-regulation. Employing assays including rubidium efflux and dopamine release, we demonstrated that these changes in receptor expression correlate with changes in receptor function. These receptor changes are believed to play an important role in nicotine dependence and withdrawal. Our recent work in this area has explored developmental differences in the receptor responses of chronic nicotine. We have found that adolescents have different patterns of receptor expression and regulation, and that males and females also exhibit some different receptor responses, especially in early developmental periods.

The other primary emphasis in the lab has been to study the effects of chronic nicotine on gene expression in brain regions, focusing on developmental differences. Chronic nicotine in adults and adolescents alters gene expression in the ventral tegmental area (VTA), a key nucleus in the brain’s dopaminergic reward pathway. In the adult, most of nicotine’s effects on gene regulation were transient (i.e. they were detectable immediately after nicotine exposure, but did not remain one month later). In contrast, adolescent rats had fewer transiently altered genes, but 5 times more genes that were persistently regulated—their expression remained altered one month after the end of nicotine exposure. These persistently altered genes included some for neuronal development, as well as genes involved in learning and memory. These results suggest that exposure to nicotine while the brain is still developing can have profound and lasting effects on gene expression in the brain’s reward pathway, that persist at least until adulthood, whereas adult exposure is far less likely to have such persistent effects. We have now extended this microarray approach to measure the genomic responses to prenatal nicotine in the VTA of adolescent offspring one month after the end of drug exposure. Such exposure caused extensive (>1000 genes) and persistent changes in gene expression; surprisingly, the effects in males and females differed greatly. More than twice as many genes were altered in males, and surprisingly only about 5% of the genes affected were the same in the two sexes. We are currently following up these findings with qtPCR validation of selected genes of interest, extending them to other brain regions, and measuring changes in protein expression and function. We believe that these findings will be important for understanding the behavioral consequences in offspring from mothers who smoke during pregnancy.

Programs

  • Pharmaceutical Sciences

Publications

View publications by this faculty member from January 1, 2013 - present

Lomazzo E, Hussmann GP, Wolfe BB, Yasuda RP, Perry DC & Kellar KJ. (2011) Effects of chronic nicotine on heteromeric nicotinic receptors in rat primary cultured neurons. J. Neurochemistry 119:153-164. doi: 10.1111/j.1471-4159.2011.07408.x PMID: 21806615; PubMed Central PMCID: PMC3171599

Doura MB, Luu TV, Lee NH & Perry DC. (2010) Persistent gene expression changes in ventral tegmental area of adolescent but not adult rats in response to chronic nicotine. Neuroscience 170:503-313. doi:10.1016/j.neuroscience.2010.06.071 PMID: 20633606; PubMed Central PMCID: PMC2962594

Gold AB, Keller AM & Perry DC. (2009) Prenatal exposure of rats to nicotine causes persistent alterations of nicotinic cholinergic receptors. Brain Research 1250: 88-100. doi.org/10.1016/j.brainres.2008.10.076 PMID: 19028470; PubMed Central PMCID: PMC2866508

Doura MB, Gold AB, Keller AB & Perry DC. (2008) Adult and periadolescent rats differ in the expression of nicotinic cholinergic receptor subtypes and in the regulation of those subtypes by chronic nicotine exposure. Brain Research 1215:40-52. doi:10.1016/j.brainres.2008.03.056 PMCID PMC2493527

Rasmussen BA, Perry DC, O’Neil J, Manaye KF & Tizabi Y. (2008) Effects of nicotine on sensorimotor gating impairment induced by long-term treatment with neurotoxic NMDA antagonism. Neurotoxicity Research 13(3,4): 151-161. PMID: 18522895

Mao D, Perry DC, Yasuda RP, Wolfe BB & Kellar KJ. (2008) The alpha4beta2alpha5 nicotinic cholinergic receptor in rat brain is resistant to up-regulation by nicotine in vivo. J. Neurochem. 104:446-456. PMID: 17961152

Perry DC, Mao D, Gold AB, McIntosh JM, Pezzullo JC, & Kellar KJ. (2007) Chronic nicotine differentially regulates alpha6- and beta3-containing nicotinic cholinergic receptors in rat brain. J. Pharmacol. Exp. Therap. 322:306-315. PMID: 17446303

Rasmussen BA, Perry DC. (2006) An autoradiographic analysis of [125I]alpha-bungarotoxin binding in rat brain after chronic nicotine exposure. Neurosci. Lett. 404:9-14. PMID: 16750882

Nguyen HN, Rasmussen BA & Perry DC. (2004) Binding and functional activity of nicotinic cholinergic receptors in selected rat brain regions are increased following long-term but not short-term nicotine treatment J. Neurochem. 90:40-49. PMID: 15198665

Nguyen HN, Rasmussen BA & Perry DC. (2003) Subtype-selective upregulation by chronic nicotine of high affinity nicotinic receptors in rat brain demonstrated by receptor autoradiography. J. Pharmacol. Exp. Therap. 307:1090-1097. PMID: 14560040

Perry DC, Dávila-García MI, Stockmeier CA & Kellar KJ (1999) Increased nicotinic receptors in brains from smokers: membrane binding and autoradiographic studies. J. Pharmacol. Exp. Therap. 289:1545-1552. PMID: 10336551

Perry DC & Kellar KJ (1995) [3H]Epibatidine labels nicotinic receptors in rat brain: an autoradiographic study. J. Pharm. Exp. Therap. 275:1030-1034. PMID: 7473129

Additional publications published before January 1, 2013 may be available within Himmelfarb Library's database.