*** These articles are required reading, and are of particular importance and interest. Graduate students are responsible for all articles.

Required Text

Buy at Amazon Cooper, Jack R., Floyd E. Bloom, and Robert H. Roth. The Biochemical Basis of Neuropharmacology. 8th ed. Oxford, UK: Oxford University Press, 2002. ISBN: 9780195140088.

1 Neurotransmitters, receptors, and actions

Cooper, Bloom, and Roth. "Introduction." Chapter 1, pp. 1-6.

———. "Cellular Foundations of Neuropharmacology." Chapter 2, pp. 7-37.

———. "Molecular Foundations of Neuropharmacology." Chapter 3, pp. 39-64.

*** Funk, C. D. "Prostaglandins and Leukotrienes: Advances in Eicosanoid Biology." Science 294 (2001): 1871-1875.

*** Corbin J. D., S. H. Francis, and D. J. Webb. "Phosphodiesterase Type 5 as a Pharmacologic Target in Erectile Dysfunction." Urology 60, 2, Suppl. 2 (2002): 4-11.

Moncada, S., and A. Higgs. "The L-Arginine-Nitric Oxide Pathway." N Engl J Med 329, no. 27 (1993): 2002-2012.

Snyder, S. H., and G. W. Pasternak. "Historical Review: Opioid Receptors." Trends Pharmacol Sci 24, no. 4 (April 2003): 198-205.

2 Membranes and the blood brain barrier

Buy at Amazon *** Laterra, J., R. Keep, L. A. Betz, and G. W. Goldstein. "Blood-Brain Barrier." In Basic Neurochemistry: Molecular, Cellular, and Medical Aspects. Edited by George J. Siegel, Bernard W. Agranoff, R. Wayne Albers, Stephen K. Fisher, and Michael D. Uhler. Baltimore, MD: Lippincott Williams & Wilkins, c1999. ISBN: 9780397518203.

Buy at Amazon *** Pardridge, W. M. "Regulation of Amino Acid Availability to the Brain." In Nutrition and the Brain. Vol. 1. Edited by R. J. Wurtman and J. J. Wurtman. New York, NY: Raven Press, 1977, pp. 142-175. ISBN: 9780890040454.

*** Wurtman, R. J., et al. "Synaptic Proteins and Phospholipids are Increased in Gerbil Brain by Administering Uridine Plus DHA Orally." Brain Research 1088 (2006): 83-92.

Kang, J. X., et al. "Fat-1 Mice Convert n-6 to n-3 Fatty Acids." Nature 427 (2004): 504.

Pooler, A., et al. "Uridine Enhances Neurite Outgrowth in NGF-Differentiated PC-12 Cells." Neuroscience 134 (2005): 207-214.

3 Acetylcholine: biochemistry

Cooper, Bloom, and Roth. "Acetylcholine." Chapter 7, pp. 151-179.

*** Ulus, I. H., R. J. Wurtman, C. Mauron, and J. K. Blusztajn. "Choline Increases Acetylcholine Release and Protects Against the Stimulation-Induced Decrease in Phosphatide Levels within Membranes of Rat Corpus Striatum." Brain Research 484 (1989): 217-227.

Wurtman, Cansev, and Ulus. "Choline and Its Products, Acetylcholine, and Phosphatidylcholine." Handbook of Neurochemistry, 2007, pp. 3-38.

4 Acetylcholine: Alzheimer's disease

Cooper, Bloom, and Roth. "Treating Neurological and Psychiatric Diseases." Chapter 13, pp. 373-400.

*** Selkoe, D. J. "Alzheimer's Disease is a Synaptic Failure." Science 298 (2002): 789-791.

Nitsch R. M., J. K. Blusztajn, A. G. Pittas, B. E. Slack, J. H. Growdon, and R. J. Wurtman. "Evidence for a Membrane Defect in Alzheimer Disease." Brain Proc Natl Acad Sci USA 89 (1992): 1671-1675.

Tuszynski, M. H., L. Thal, M. Pay, D. P. Salmon, U HS, R. Bakay, P. Patel, A. Blesch, H. L. Vahlsing, Ho G, G. Tong, S. G. Potkin, J. Fallon, L. Hansen, E. J. Mufson, J. H. Kordower, C. Gall, and J. Conner. "A Phase 1 Clinical Trial of Nerve Growth Factor Gene Therapy for Alzheimer Disease." Nat Med 11, no. 5 (May 2005): 551-555.

5 Dopamine: biochemistry and Parkinson's disease

Cooper, Bloom, and Roth. "Dopamine." Chapter 9, pp. 225-270.

———. "Treating Neurological and Psychiatric Diseases." Chapter 13, pp. 373-400.

*** Hokfelt, T., J. F. Rehfeld, L. Skirboll, B. Ivemark, M. Goldstein, and K. Markey. "Evidence for Coexistence of Dopamine and CCK in Meso-Limbic Neurones." Nature 285 (1980): 476-477.

*** Burns, R. S., P. A. LeWitt, M. H. Ebert, H. Pakkenberg, and I. J. Kopin. "The Clinical Syndrome of Striatal Dopamine Deficiency." N Engl J Med 312, no. 22 (1985): 1418-1421.

*** Acworth, I. N., M. J. During, and R. J. Wurtman. "Tyrosine: Effects on Catecholamine Release." Brain Res Bull 21, no. 3 (1988): 473-477.

Bezard, E., S. Ferry, U. Mach, H. Stark, L. Leriche, T. Boraud, C. Gross, and P. Sokoloff. "Attenuation of Levodopa-Induced Dyskinesia by Normalizing Dopamine D(3) Receptor Function." Nat Med 9, no. 6 (2003): 762-767.

Knecht, S., C. Breitenstein, S. Bushuven, S. Wailke, S. Kamping, A. Floel, P. Zwitserlood, and E. B. Ringelstein. "Levodopa: Faster and Better Word Learning in Normal Humans." Ann Neurol 56, no. 1 (July 2004): 20-26.

Cansev, M., and R. J. Wurtman. "Aromatic Amino Acids." In Handbook of Neurochemistry and Molecular Neurobiology. Vol. 6, chapter 3, 2006, pp. 60-97.

6 Norepinephrine and epinephrine

Cooper, Bloom, and Roth. "Norepinephrine and Epinephrine." Chapter 8, pp. 181-223.

———. "Treating Neurological and Psychiatric Diseases." Chapter 13, pp. 373-400.

*** Wurtman, R. J., and J. Axelrod. "Control of Enzymatic Synthesis of Adrenaline in the Adrenal Medulla by Adrenal Cortical Steroids." J Biol Chem 241, no. 10 (1966): 2301-2305.

*** Berridge, C. W., and B. D. Waterhouse. "The Locus Coeruleus-Noradrenergic System: Modulation of Behavioral State and State-Dependent Cognitive Processes." Brain Res Rev 42 (2003): 33-84.

Insel, P. A. "Adrenergic Receptors-Evolving Concepts and Clinical Implications." N Engl J Med 334, no. 9 (1996): 580-585.

Melamed, E., F. Hefti, and R. J. Wurtman. "Tyrosine Administration Increases Striatal Dopamine Release in Rats with Partial Nigrostriatal Lesions." PNAS 77, no. 7 (1980): 4305-4309.

Conlay, L. A., T. J. Maher, and R. J. Wurtman. "Tyrosine Increases Blood Pressure in Hypotensive Rats." Science 212, no. 4494 (1981): 559-560.

7 Serotonin: biochemistry

Cooper, Bloom, and Roth. "Serotonin, Histamine, and Adenosine." Chapter 10, pp. 271-304.

———. "Treating Neurological and Psychiatric Diseases." Chapter 13, pp. 373-400.

*** Fernstrom, J. D., and R. J. Wurtman. "Brain Serotonin Content: Physiological Dependence on Plasma Tryptophan Levels." Science 173 (1971): 149-152.

*** ———. "Brain Serotonin Content: Physiological Regulation by Plasma Neutral Amino Acids." Science 178 (1972): 414-416.

*** Wurtman, R. J., and J. J. Wurtman. "Carbohydrates and Depression." Scientific American 1 (1989): 68-75.

*** Schaechter, J. D., and R. J. Wurtman. "Tryptophan Availability Modulates Serotonin Release from Rat Hypothalamic Slices." J Neurochem 53, no. 6 (1989): 1925-1933.

*** Wurtman, R. J., J. J. Wurtman, M. M. Regan, J. M. McDermott, R. H. Tsay, and J. J. Breu. "Effects of Normal Meals Rich in Carbohydrates or Proteins on Plasma Tryptophan and Tyrosine Ratios." Am J Clin Nutr 77, no. 1 (January 2003): 128-132.

Fernstrom, J. D., and R. J. Wurtman. "Brain Serotonin Content: Increase Following Ingestion of Carbohydrate Diet." Science 174 (1971): 1023-1025.

8 Serotonin: behavior, and obesity

*** Nishizawa, S., C. Benkelfat, S. N. Young, M. Leyton, S. Mzengeza, C. de Montigny, P. Blier, and M. Diksic. "Differences between Males and Females in Rates of Serotonin Synthesis in Human Brain." Proc Natl Acad Sci USA 94 (1997): 5308-5313.

*** Austin, M. C., R. E. Whitehead, C. L. Edgar, J. E. Januaryosky, and D. A. Lewis. "Localized Decrease in Serotonin Transporter-Immunoreactive Axons in the Prefrontal Cortex of Depressed Subjects Committing Suicide." Neuroscience 114, no. 3 (2002): 807-815.

*** Caspi, A., K. Sugden, T. E. Moffitt, A. Taylor, I. W. Craig, H. Harrington, J. McClay, J. Mill, J. Martin, A. Braithwaite, and R. Poulton. "Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene." Science 301, no. 5631 (2003): 386-389.

*** Fava, M., and K. S. Kendler. "Major Depressive Disorder." Neuron 28, no. 2: 335-341.

Zhang, X., R. R. Gainetdinov, J. M. Beaulieu, T. D. Sotnikova, L. H. Burch, R. B. Williams, D. A. Schwartz, K. R. Krishnan, and M. G. Caron. "Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major Depression." Neuron 45, no. 1 (January 6, 2005): 11-16.

"Zelnorm gets US FDA OK for Chronic Constipation." SCRIP (August 27, 2004).

"The Link Between Ecstasy, Depression and Genetics." The Economist (March 21, 2005).

Wurtman, J. J., and R. J. Wurtman. "D-Fenfluramine Selectively Decreases Carbohydrate But Not Protein Intake in Obese Subjects." Intl J Obesity 8, no. 1 (1984): 79-84.

Meltzer, H. "Illuminating the Molecular Basis for Some Antipsychotic Drug-Induced Metabolic Burden." PNAS 104 (2007): 3019-3020.

9 Review  
10 Hour examination - midterm  
11 Melatonin

*** Wurtman, R. J. "Melatonin." Encyclopedia of Dietary Supplements, 2005, pp. 457-466.

Wurtman, R. J., J. Axelrod, and Chu E. W. "Melatonin, A Pineal Substance: Effect on the Rat Ovary." Science 141 (1963): 277-278.

Lynch, H. J., R. J. Wurtman, M. A. Moskowitz, M. C. Archer, and M. H. Ho. "Daily Rhythm in the Human Urinary Melatonin." Science 187 (1975): 169-171.

Zhdanova, I. V., R. J. Wurtman, M. M. Regan, J. A. Taylor, J. P. Shi, and O. U. Leclair. "Melatonin Treatment for Age-Related Insomnia." J Clin Endocrin Metab 86, no. 10 (2001): 4727-4730.

Gerdin, M. J., M. I. Masana, M. A. Rivera-Bermudez, R. L. Hudson, D. J. Earnest, M. U. Gillette, and M. L. Dubocovich. "Melatonin Desensitizes Endogenous MT2 Melatonin Receptors in the Rat Suprachiasmatic Nucleus: Relevance for Defining the Periods of Sensitivity of the Mammalian Circadian Clock to Melatonin." FASEB J 18, no. 14 (November 2004): 1646-1656.

Wurtman, R. J. "Ramelteon: A Novel Treatment for the Treatment of Insomnia." Expert RSV Neurother 6 (2006): 957-964.

12-13 Glutamate: biochemistry, learning and toxicity

Cooper, Bloom, and Roth. "Molecular Foundations of Neuropharmacology." Chapter 3, pp. 59-64.

———. "Modulation of Synaptic Transmission." Chapter 5, pp. 85-104.

———. "Amino Acid Transmitters." Chapter 6, pp. 132-150.

———. "Cellular Mechanisms in Learning and Memory." Chapter 12, pp. 357-372.

*** Mothet, J. P., A. T. Parent, H. Wolosker, R. O. Brady Jr., D. J. Linden, C. D. Ferris, M. A. Rogawski, and S. H. Snyder. "D-Serine is an Endogenous Ligand for the Glycine Site of the N-Methyl-D-Aspartate Receptor." Proc Natl Acad Science USA 97, no. 9 (2000): 4926-4931.

*** Malenka, R. C., and M. F. Bear. "LTP and LTD: An Embarrassment of Riches." Neuron 44, no. 1 (September 30, 2004): 5-21.

*** Südhof, T. C. "The Synaptic Vesicle Cycle Revisited." Neuron 28, no. 2 (2000): 317-320.

Krystal, J. H., et al. "NMDA Agonists and Antagonists as Probes of Glutamatergic Dysfunction and Pharmacotherapies in Neuropsychiatric Disorders." Harvard Rev Psychiatry 7 (1999): 125-143.

Fon, E. A., and R. H. Edwards. "Molecular Mechanisms of Neurotransmitter Release." Muscle Nerve 24, no. 5 (2001): 581-601.

14 GABA: anxiety, seizures

Cooper, Bloom, and Roth. "Amino Acid Transmitters." Chapter 6, pp. 105-132.

*** Gale, K., and M. J. Iadarola. "Seizure Protection and Increased Nerve-Terminal GABA: Delayed Effects of GABA Transmission Inhibition." Science 208 (1980): 288-291.

Wang, L., T. J. Maher, and R. J. Wurtman. "Oral L-Glutamine Increases GABA Levels in Striatal Tissue and Extracellular Fluid." FASB J 21 (2007): 1227-1232.

Nie, Z., P. Schweitzer, A. J. Roberts, S. G. Madamba, S. D. Moore, and G. R. Siggins. "Ethanol Augments GABAergic Transmission in the Central Amygdala via CRF1 Receptors." Science 303, no. 5663 (March 5, 2004): 1512-1514.

15 Glycine and histamine

Cooper, Bloom, and Roth. "Serotonin, Histamine, and Adenosine." Chapter 10, pp. 304-320.

*** Betz, H., and C. M. Becker. "The Mammalian Glycine Receptor: Biology and Structure of a Neuronal Chloride Channel Protein." Neurochem Int 13, no. 2 (1988): 137-146.

*** Anagnostaras, S. G., M. G. Craske, and M. S. Fanselow. "Anxiety: At the Intersection of Genes and Experience." Nature Neurosci 2, no. 9 (1999): 780-782.

*** Shankley, N. P., G. F. Watt, and J. W. Black. "Definition and Localization of Histamine H2 Receptors." Euro J Clin Investig 25, no. 1 (1995): 12-18.

Rogawski, M. A. "Progesterone, Neurosteroids, and the Hormonal Basis of Catamenial Epilepsy." Ann Neurol 53, no. 3 (2003): 288-290.

Simons, F. E. R., and K. J. Simons. "The Pharmacology and Use of H1-Receptor-Antagonist Drugs." New England J Med 330, no. 23 (1994): 1663-1670.

Masaki, T., S. Chiba, G. Yoshimichi, T. Yasuda, H. Noguchi, T. Kakuma, T. Sakata, and H. Yoshimatsu. "Neuronal Histamine Regulates Food Intake, Adiposity, and Uncoupling Protein Expression in Agouti Yellow (A(y)/a) Obese Mice." Endocrinology 144, no. 6 (2003): 2741-2748.

16 Cannabinoids and adenosine

Cooper, Bloom, and Roth. "Serotonin, Histamine, and Adenosine." Chapter 10, pp. 317-320.

*** Fredholm, B. B. "Adenosine Receptors in the Central Nervous System." NIPS 10 (1995): 122-128.

*** Goutopoulos, A., and A. Makriyannis. "From Cannabis to Cannabinergics: New Therapeutic Opportunities." Pharmacol Ther 95, no. 2 (2002): 103-117.

*** Wilson, R. I., and R. A. Nicoll. "Endocannabinoid Signaling in the Brain." Science 296, no. 5568 (2002): 678-682.

Conlay, L. A., J. A. Conant, F. deBros, and R. J. Wurtman. "Caffeine Alters Plasma Adenosine Levels." Nature 389 (1997): 136.

17 Brain peptides

Cooper, Bloom, and Roth. "Neuroactive Peptides." Chapter 11, pp. 321-356.

*** Nichols, M. L., et al. "Transmission of Chronic Nociception by Spinal Neurons Expressing the Substance P Receptor." Science 268 (1999): 1558-1561.

*** Selmer, I-S., M. Schindler, J. P. Allen, P. P. A. Humphrey, and P.C. Emson. "Advances in Understanding Neuronal Somatostatin Receptors." Regulatory Peptides 90 (2000): 1-18.

*** Degen, L., D. Matzinger, J. Drewe, and C. Beglinger. "The Effect of Cholecystokinin in Controlling Appetite and Food Intake in Humans." Peptides 22, no. 8 (2001): 1265-1269.

Schwartz, M. W., S. C. Woods, D. Porte Jr., R. J. Seeley, and D. G. Baskin. "Central Nervous System Control of Food Intake." Nature 404 (2000): 661-671.

Wurtman, R. J. "Narcolepsy and the Hypocretins." Metabolism 55 (2006): 536-539.

18 Drug development and review

Cooper, Bloom, and Roth. "Treating Neurological and Psychiatric Diseases." Chapter 13, pp. 373-400.

*** Wurtman, R. J., and R. L. Bettiker. "The Slowing of Treatment Discovery, 1965-1995." Nat Med 1, no. 11 (1995): 1122-1125.

*** Wurtman, R. J. "What Went Right: Why is HIV a Treatable Infection?" Nat Med 3, no. 7 (1997): 714-717.

19 Hour examination - final