• B.A. in Biochemical Sciences, Harvard College, 1970
• Ph.D. in Pharmaceutical Chemistry, University of California, San Francisco, 1981
• Postdoc in Neuroscience, Johns Hopkins (lab of Dr. Solomon H. Snyder), 1983

Left to Right: Menahem Doura, Ashleigh Keller, Dr. David Perry, Shuba Sankaran (Georgetown), and Bruce Rasmussen

• Neuronal nicotinic receptors; nicotinic neurobiology; nicotine addiction; drugs of abuse; autoradiography

The research in my lab is aimed at understanding the roles of neuronal nicotinic cholinergic receptors in neurotransmission, disease and in mediating nicotine addiction.  Of particular interest to us is elucidating how different subtypes of nicotinic receptors contribute to these processes.  Our principal effort recently has been in receptor autoradiography.  Along with Dr. Ken Kellar of Georgetown University, we pioneered the use of several new radioligands to label nicotinic receptors, including [³H]epibatidine, [¹²⁵I]epibatidine and [¹²⁵I]A-85380.  By combining our knowledge of how these ligands bind to receptor subunits expressed in clonal cell lines, with their pattern of labeling in brain sections, we have developed a novel quantitative approach to measure receptor subtypes with autoradiography.  This method allows us to measure different subtypes even in small nuclei in the brain and other tissues; using this approach in rat, we have detected not only the major subtypes of a4b2 and a7, but also subtypes with a more limited distribution, including one with properties of a3b4 receptors and another with properties of  a3/a6b2 receptors.
     An important approach to understanding nicotine addiction is to study the effects of chronic nicotine administration on the brain.  We used autoradiographic methods to demonstrate that nicotinic receptors are greatly up-regulated in brains from human smokers.  This up-regulation may help mediate the neurobiological changes associated with nicotine addiction.  We have recently applied our new quantitative autoradiographic methods to show that subtypes of nicotinic receptors are differentially affected by chronic nicotine.  This may contribute to an altered pattern of response of experienced smokers compared to naive users.  There is controversy over whether up-regulated nicotinic receptors correspond to an increase in functional activity, or whether they are composed largely of inactivated receptor sites.  To address this question, we employed the rubidium efflux method to measure changes in receptor function following chronic nicotine exposure.  We found that while exposure to nicotine overnight had no effect, two week exposure caused an increase in rubidium efflux in some regions (cerebral cortex, superior colliculus), but no change in others.  This increased functional activity appeared to be largely limited to the a4b2 subtype.  Our current studies are focused on extending these findings to determine the onset of these changes and the rate of recovery.  We are also interested in the changes in gene expression that occur during chronic nicotine exposure. 
     Neuronal nicotinic receptors play a variety of important roles, in both physiological and pathological states.  For instance, The very high rate of smoking among schizophrenics is one piece of evidence for a role for nicotinic receptors in this disease.  We are using animal models to study this in collaboration with Dr. Yousef Tizabi of Howard University.  Other areas of interest include nicotine and tobacco in pregnancy, in collaboration with the District of Columbia Initiative.

Dαvila-Garcνa MI, Musachio JL, Perry DC, Xiao Y, Horti A, London ED, Dannals RF & Kellar KJ (1997)  [¹²⁵I]IPH, an epibatidine analog, binds with high affinity to neuronal nicotinic cholinergic receptors. J. Pharmacol. Exp. Therap. 82:445-451. 

Perry DC, Dαvila-Garcνa 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. 

Tizabi Y, Russell, LT, Nespor SM, Perry DC & Grunberg NE (2000) Prenatal nicotine exposure: Effects on locomotor activity and central [¹²⁵I]a-bungarotoxin binding in rats. Pharm. Biochem Behav. 66:495-500. 

Tizabi Y & Perry D (2000) Prenatal nicotine exposure: Effects on [¹²⁵I]epibatidine binding in rat brain.  Pharmacol. Biochem. Behav. 67:319-323. 

Ferreira M, Ebert SN, Perry DC, Yasuda RP, Baker C, Davila-Garcia MI, Kellar KJ & Gillis, RA (2001)  Evidence of a functional a7 neuronal nicotinic receptor subtype located on motoneurons of the dorsal motor nucleus of the vagus.  J. Pharmacol. Exp. Therap. 296:260-269. 

Perry DC, Xiao Y, Nguyen HN, Musachio JL, Davila-Garcia MI & Kellar KJ, (2002) Measuring nicotinic receptors with characteristics of a4β2, a3β2 and a3β4 subtypes in rat tissues by autoradiography. J. Neurochemistry 82:468-481. 

Nguyen HN, Rasmussen BE & 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. 

Nguyen HN, Rasmussen BE & 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. Neurochemistry 90:40-49

For a Medline search for other publications of Dr. Perry’s, click HERE

Children: 
  Ragani Harris, Art Director, ApotheCom Associates, LLC 

   Michael Perry  Technician, Ourisman Honda

   Lisa Perry     Walt Whitman H.S. Chamber Singers