The research in Dr. Buccafusco's laboratory includes the development of novel treatment modalities for Alzheimer's disease and related disorders. In 1988 his laboratory was the first to report the cognitive enhancing action of low doses of nicotine in non-human primates. Since that time he has studied numerous novel memory-enhancing agents from several pharmacological classes in young and aged Rhesus monkeys. His most recent work is directed at the development of single molecular entities that act on multiple CNS targets to, not only enhance cognitive function, but also to provide neuroprotection, or to alter the disposition and metabolism of amyloid precursor protein.
Dr. Buccafusco also has studied the toxic effects of organophosphorus anticholinesterases used as insecticides and as chemical warfare agents. In particular, he has studied the behavioral/cognitive alterations associated with low level, chronic exposure to such agents. His work in the area of drug abuse has centered around the role of central cholinergic neurons in the development of physical dependence on opiates, and the in the expression of withdrawal symptoms and the return to drug-seeking behavior. Most recently his laboratory is investigating the role of the immune system and in the production of auto-antibodies to beta-amyloid and to the receptor for advanced glycation end products (RAGE) by individuals with Alzheimer's disease. These studies have been supported by continuous federally-sponsored grants and by several private foundations and commercial interests.
ABBOTT, Animal Behavior Center: Delayed Matching-to-Sample for Drug Studies- Operant Testing in Macaque Subjects General Procedures,
dated February 22, 2007, for Compound A-918446. $75,600
ABBOTT, Animal Behavior Center: Delayed Matching-to-Sample for Drug Studies- Operant Testing in Macaque Subjects General Procedures,
dated June 4, 2007, for Discovery Compounds. $187,350
Institut de Recherches Servier, Research Studies in Order to Evaluate the Behavioral Effects of Servier's Cognitive Enhancing Compounds in Six Aged Rhesus Monkeys. $325,500
ABBOTT, Animal Behavior Center- New Drug Testing in Primate Models of Learning and Memory: Delayed Matching-to-Sample for Drug Studies- Operant Testing in Macaque Subjects General Procedures,
dated October 10, 2007, for Compound ABT-384. $75,600
NIH, Cotinine for Cognitive Impairment in Neurological and Neuropsychiatric Disorders. $301,350
Institute for the Study of Aging, New Drugs for Treating the Cognitive Deficits and Psychotic Symptoms of Alzheimer's Disease. $75,000
All of the above projects are ongoing in the lab.
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The New Investigator Award, National Institute on Drug Abuse, 1980.
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Sandoz Distinguished Lecturer, 1983.
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Distinguished Faculty Award for the Basic Sciences, School of Medicine (Medical College of Georgia), 1988; Callaway Foundation of Georgia, Center Grant recipient, 1989.
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Distinguished Alumnus Award, University of Medicine and Dentistry of New Jersey, 1998.
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Pharmacia- ASPET Award in Experimental Therapeutics 2008.
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VAMC Career Research Scientist of the Year 2008.
Selected from list post 1990
Symposium-in association with the American Academy of Neurology: "Assessing the Effects of Pharmacologic Agents on Cognition and on the EEG", Boston, MA Division of Neuroscience,1990.
Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ
Division of Pharmacology, Burroughs Wellcome Co., Research Triangle Park, NC
Symposium speaker - Southeastern Regional Society of Toxicology, UGA
Abbott Laboratories, Neuroscience Research, Abbott Park, IL
Gentile Pharmaceutical Company, Pizza, Italy
Department of Pharmacology, Temple University, Philadelphia,PA
Department of Neuroscience, Yerkes Regional Primate Center, Atlanta, GA
Department of Neuroscience, Lilly Laboratories, Indianapolis, IN
Department of Pharmacology and Therapeutics and Center for the Neurobiology of Aging, University of Florida, Gainesville
Georgia Research Alliance, Atlanta, GA
Division of Environmental Health Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention Public Health Service, Atlanta, GA
Emory University, Department of Pharmacology, Atlanta,GA
Boehringer Ingelheim Pharma AG (Mainz Germany)
University of Georgia School of Pharmacy, Athens, GA
Pharmacia/UpJohn, Neurobiology Division, Kalamazoo, MI
American Society for Pharmacology and Experimental Therapeutics - Retreat on Systems and Integrated Pharmacology, Rockville, MD. Role: Panel Participant
Wright State University, Department of Pharmacology and Toxicology, Dayton, OH
Memory Pharmaceuticals, Montvale, NJ
Abbott Pharmaceuticals, Abbott Park, IL
University of Kentucky, Department of Anatomy and Neurobiology, Lexington, KY
University of Kansas, Dept. Pharmacology, Toxicology & Therapeutics, Kansas City, MO
Southeastern American Association for Laboratory Animal Science - Annual Meeting, 2004; "Non-Human Primate Enrichment".
Behavioral Science Foundation, St. Kitts, EC
Pfizer Pharmaceuticals, Ann Arbor, MI
FASEB Summer Research Conference on Neurotransmitters, Saxtons River, Vermont.
Conference on Dynamics of Cholinergic Function, Oglebay Park, West Virginia
Conference on Molecular Basis of Cholinergic Function, Buxton, Derbyshire, U.K
Symposium on Brain Acetylcholine, From Preclinical to Clinical Investigations, Taormina, Italy
Island Neuroscience Research Conference, Cayman Brac
Society of Neuroscience, "Insights into Brain and Spinal Components of the Opiate Withdrawal Syndrome", NewOrleans, Louisiana
32nd IUPS Meeting, Glasgow, Symposium: Central Autonomic Mechanisms
Second Annual Duke Nicotine Research Conference, Duke University
Chemical Weapons Working Group Conference, Silver Spring, MD
Behavioral Toxicology Society Meeting, Palm Beach, FL
Fourth Annual Duke Nicotine Research Conference, Duke University
American Association of Pharmaceutical Scientists Southeast Regional Meeting, Research Triangle Park, NC
National Institutes on Aging, "Age-Related Neurobehavioral Research: An Integrative Cognitive Neuroscience Agenda for the 21st Century", Bethesda, MD
3rd International Neurodegeneration in Alzheimer's Disease, Parkinson's Disease & Acute Stroke, Princeton, NJ
Fifth Annual Duke Nicotine Research Conference, Duke University
Nonhuman Primate Models of Aging: Evaluating Their Current Status and Future Potential, Madison, WI
Institute for the Study of Aging, Second Annual Investigator's Meeting, Ryebrook, NY
Successful Aging: Exploring Interventions for Maximizing Lifespan and Healthspan. Preconference Symposium: Nonhuman Primate Models of Aging: Evaluating Their Current Status and Future Potential, Madison, WI, Title of presentation: "Pharmacological Manipulation of Memory Performance in Aged Monkeys".
5th International Neurodegeneration in Alzheimer's Disease, Parkinson's Disease & Related Disorders, Princeton, NJ. Title of presentation: "Relationship Between the Induction of Cell-Surface Antigen and the Expression of Amyloid Binding Sites and Circulating Anti-Ab42 Peptide".
Experimental Biology '03, ASPET Symposium - Nicotinic Receptors: Connecting Basic Science to Therapuetic Potential, Title of presentation - "Nicotinic Drugs Increase Learning and Memory in Non-Human Primates"; also serving as symposium co-Chair.
Institute for the Study of Aging 3rd Annual Investigator's Meeting 2002. "Drug Discovery for Alzheimer's Disease". Teaneck, NJ
Institute for the Study of Aging 4th Annual Investigator's Meeting 2003. Teaneck, NJ
Novartis OAB ATLAS Concesus Meeting 2004, NY, NY. "Muscarinic Receptors and the Heart"
Experimental Biology '04, ASPET Symposium - Pharmacology of ADHD; title of presentation: "New Therapeutic Targets and Animal Models of ADHD"
Experimental Biology '04, ASPET Public Affairs Workshop - Sustaining Integrative and Organ Systems Sciences: Problems, Opportunities, Solutions; title of presentation: "Pharmaceutical Outsourcing Preclinical Studies and Interactions with Academic Scientists"
Winter Conference on Neural Plasticity (16th Annual Meeting, in St. Lucia); "Cognition-enhancing Drugs and Learning and Memory in Primates"
Conference Chair: Emerging Molecular Targets to Treat Disorders Affecting Cognitive Function, Princeton, NJ, "Cognitive Enhancing Drugs Today: Current Products, Future Developments"
Institute for the Study of Aging Workshop, New York Academy of Sciences, Sep. 3-4, 2004; title of presentation: "Novel Analogs of Choline as Potential Neuroprotective Agents"
7th International Neurodegeneration in Alzheimer's Disease; Parkinson's Disease & Related Disorders; Princeton, NJ, Title of presentation: "Autoimmunity in Alzheimer's Disease: Increased Levels of Circulating IgGs Binding Ab and RAGE Peptides".
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(from 202 full manuscripts, books edited, book chapters, and US patents).
Buccafusco, J.J.: Mechanism of the clonidine-induced protection against acetylcholinesterase inhibitor toxicity. J. Pharmacol. Exp. Ther. 222:595-599, 1982.
Kirby, M.L. Aronstam, R.S. and Buccafusco, J.J.: Changes in cholinergic parameters associated with failure of cronotruncal septation in embryonic chick hearts after neural crest ablation. Circ. Res. 56:392-401, 1985.
Buccafusco, J.J. and Brezenoff, H.E.: Brain neurotransmitters and the development and maintenance of experimental hypertension. Prog. Drug. Res. 30:127-150, 1986.
Marshall, D.C. and Buccafusco, J.J.: Spinal cholinergic neurons and the expression of morphine withdrawal symptoms in the rat. J. Neurosci. 7:621-628, 1987.
Elrod, K., Buccafusco, J.J. and Jackson, W.J.: Nicotine enhances delayed matching-to-sample performance by primates. Life Sci. 43:277-287, 1988.
Buccafusco, J.J.: Participation of different brain regions in the anti-narcotic withdrawal action of clonidine in the dependent rat. Brain Res. 513:8-14, 1990.
Buccafusco, J.J. and Jackson, W.J.: Beneficial effects of nicotine administered prior to a delayed matching-to-sample task in young and aged monkeys. Neurobiol. Aging 12:233-238, 1991.
Takahashi, H. and Buccafusco, J.J.: Excitatory modulation by a spinal cholinergic system of a descending sympathoexcitatory pathway in rats. Neuropharmacology 31:259-269, 1992.
Buccafusco, J.J.: Neuropharmacologic and behavioral actions of clonidine: Interactions with central neurotransmitters. International Rev. Neurobiol. 33:55-107, 1992.
Terry, A.V., Jr., Jackson, W.J. and Buccafusco, J.J.: Effects of concomitant cholinergic and adrenergic stimulation on learning and memory performance by young and aged monkeys. Cerebral Cortex, 3:304-312, 1993.
Wei, J., Milici, A. and Buccafusco, J.J.: Alterations in the expression of the genes encoding specific muscarinic receptor subtypes in the hypothalamus of spontaneously hypertensive rats. Circ. Res. 76:142-146, 1995.
Buccafusco, J.J.: The role of central cholinergic neurons in the regulation of blood pressure and in experimental hypertension. Pharmacol. Rev. 48: 179-211, 1996.
Prendergast, M.A., Jackson, W.J., Terry, A.V., Jr., Kille, N.J., Arneric, S.P. and Buccafusco, J.J.: Age-related: differences in distractibility and response to methylphenidate in monkeys. Cerebral Cortex 8: 164-172, 1998.
Terry, A.V., Jr., Buccafusco, J.J., Jackson, W.J., Prendergast, M.A., Fontana, D.J., Wong, E.H., Bonhaus, D.W., Weller, P. and Eglen, R.M.: Enhanced delayed matching performance in younger and older macaques administered the 5-HT4 receptor agonist, RS 17017. Psychopharmacology 135: 407-415, 1998.
Zhang, L.C. and Buccafusco, J.J.: Adaptive changes in the expression M1 muscarinic receptors during and after morphine withdrawal: localization to areas of cognition and memory. Neuropharmacology 39: 1720-1731, 2000.
Jonnala, R.R., Graham, J.H., III, Terry, A.V., Jr., Beach, J.W., Young, J.A. and Buccafusco, J.J.: Relative levels of cytoprotection produced by analogs of choline and the role of a7-nicotinic acetylcholine receptors. Synapse 47: 262-269, 2003.
Mruthinti, S., Buccafusco, J.J., Hill, W.D., Waller, J.L., Jackson, T.W., Zamrini, E.Y. and Schade, R.F.: Autoimmunity in Alzheimer's disease: Increased levels of circulating IgGs binding Ab and RAGE peptides. Neurobiol. Aging 25: 1023-1032, 2004.
Buccafusco, J.J.: Neuronal nicotinic receptor subtypes: defining therapeutic targets. Mol. Interventions 4: 285-295, 2004.
Buccafusco, J.J., Letchworth, S.R., Bencherif, M. and Lippillo, P.M.: Long-lasting cognitive improvement with nicotinic receptor agonists: mechanisms of pharmacokinetic-pharmacodynamic discordance. Trends in Pharmacological Sci. 26: 352-360, 2005.
Terry, A.V., Jr., Hernandez, C.M., Hohnadel, E.J., Bouchard, K.P. and Buccafusco, J.J.: Cotinine, a neuroactive metabolite of nicotine: potential for treating disorders of impaired cognition. CNS Drug Rev. 11: 229-252, 2005.
Youdim, M.B.H. and Buccafusco, J.J.: CNS targets for multi-functional drugs in the treatment of neurodegenerative diseases. J. Neural Transm. 112: 519-537, 2005.
Terry, A.V., Jr., Buccafusco, J.J. and Bartoszyk, G.D.: Selective Serotonin 5HT2A Antagonist EMD 281014 Improves Delayed Matching Performance in Young and Aged Rhesus Monkeys. Psychopharmacology 179: 725-732, 2005.
Graham, J.H., Papke, R.L. and Buccafusco, J.J.: Functional central nicotinic acetylcholine receptor antagonism by systemic administration of Tinuvin 770 (BTMPS). Current Alzheimer Res. 2: 141-147, 2005.
De Luca, C.J., Buccafusco, J.J., Roy, S.H, De Luca, G., and Nawab, H.: The electromyographic signal as a presymptomatic indicator of organophosphates in the body. Muscle & Nerve 33: 369-376, 2006.
Schechter, L.E., Smith, D.L., Rosenzweig-Lipson, S., Sukoff, S., Dawson, L.A., Marquis, K., Jones, D., Piesla, M., Andree, T., Nawoschik, S., Harder, J.A., Womack, M.D., Buccafusco, J.J., Terry, A.V., Hoebel, B., Rada, P., Kelly, M., Abou-Gharbia, M., Barrett, J.E., Childers, W.: Lecozotan (SRA-333): A selective serotonin 1A receptor antagonist that enhances the stimulated release of glutamate and acetylcholine in the hippocampus and promotes procognitive effects. J. Pharmacol. Exp. Ther. 314: 1274-1289, 2005.
Li, X.D., Arias, E., Jonnala, R.R., Mruthinti, S. and, Buccafusco, J.J.: Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo. J. Mol. Neurosci. 27: 325-336, 2005.
Buccafusco, J.J., Shuster, L.C. and Terry, A.V., Jr., Disconnection between activation and desensitization of autonomic nicotinic receptors by nicotine and cotinine. Neurosci Letts 413: 68-71, 2007.
Matta, S.G., Balfour, D.J., Benowitz, N.L., Boyd, T., Buccafusco, J.J., Caggiula, A.R., Craig, C.R., Collins, A.C., Damaj, M.I., Donny, E.C., Gardiner, P.S., Grady, S.R., Heberlein, U., Leonard, S.S., Levin, E.D., Lukas, R.J., Markou, A., Marks, M.J., McCallum, S.E., Parameswaran, N., Perkins, K.A., Picciotto, M.R., Quik, M., Rose, J.E., Rothenfluh, A., Schafer, W.R., Stolerman, I.P., Tyndale, R.F., Wehner, J.M. and Zirger, J.M., Guidelines on nicotine dose selection for in vivo research. Psychopharmacology 190: 269-319, 2007.
Buccafusco, J.J. and Bain, J.N., A 24-hour access i.v. self-administration schedule of morphine reinforcement and the estimation of recidivism: pharmacological modification by arecoline. Neuroscience 149: 487-489, 2007.
Mruthinti, S., Capito, N., Sood, A. and Buccafusco, J.J., Cytotoxicity of Ab1-42, RAGE23-54, and an Ab-RAGE complex in PC-12 cells. Current Alzheimer Res. 4: 581-586, 2007.
Buccafusco, J.J., Powers, J.C., Hernandez, M.A., Prendergast, M.A., Terry, A.V., Jr. and Jonnala, R.R, MHP-133, a drug with multiple CNS targets: potential for neuroprotection and enhanced cognition. Neurochem. Res. 32:1224-1237, 2007.
Sood, A., Beach, J.W., Webster, S.J., Terry, Jr., A.V. and Buccafusco, J.J., The effects of JWB1-84-1 on memory-related task performance by amyloid Ab transgenic mice and by young and aged monkeys. Neuropharmacology 53: 588-600, 2007.
Buccafusco, J.J., Terry, Jr., A.V., Decker, M.W. and Gopalakrishnan, M, Profile of nicotinic acetylcholine receptor agonists ABT-594 and A-582941, with differential subtype selectivity, on delayed matching accuracy by young monkeys. Biochem. Pharmacol. 74: 1202-1211, 2007.
Bitner, R.S., Bunnelle, W.H., Anderson, D.J., Buccafusco, J., Curzon, P., Decker, M.W., Frost, J.M., Halvard Gronlein, J., Gubbins, E., Li, J., Malysz, J., Markosyan, S., Marsh, K., Meyer, M.D., Nikkel, A., Radek, R.J., Robb, H.M., Timmermans, D., Sullivan, J.P., and Gopalakrishnan, M., Broad spectrum efficacy across cognitive domains by a7 nicotinic acetylcholine receptor agonism correlates with activation of erk1/2 and creb phosphorylation pathways. J. Neurosci. 27: 10578-10587, 2007.
Levin, E.D. and Buccafusco, J.J.: Animal Models of Cognitive Impairment, CRC Press, New York, 2006.
Buccafusco, J.J: Cognitive pharmacology in aging macaques. In, Animal Models of Cognitive Impairment, eds E. Levin and J.J. Buccafusco, CRC Press, New York, 2006, pp. 285-300.
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