The primary goal of the Laboratory of Neuropsychopharmacology is to understand the molecular basis of complex psychiatric diseases including depression, anxiety disorders and schizophrenia with a particular focus on neuropeptides. To address these issues, we use a variety of behavioral, pharmacological and molecular techniques.
Our laboratory has been particularly interested in the neurobiology of depression and anxiety disorders. Our lab was the first to identify elevated levels of corticotropin-releasing factor (CRF) in depressed patients. Since then, our lab has been one of the driving forces in understanding the role CRF may play in the pathophysiology and treatment of mood and anxiety disorders. We have demonstrated that chronic administration of a number of antidepressants, benzodiazepines, as well as mood stabilizers all interact with the CRF system. We are currently investigating the behavioral, endocrine, and pharmacologic effects associated with acute and chronic treatment with CRF1 receptor antagonists in rodents. These compounds show great potential as novel antidepressants and/or anxiolytics. These studies employ a variety of behavioral, endocrinological, and molecular techniques, and we are currently exploring the use of gene arrays to identify novel behaviorally-relevant genes.
We also use analogous methodologies to explore the mechanism of action of antipsychotic drugs and the pathogenesis of schizophrenia. Currently, antipsychotic drugs are not completely effective and their ultimate mechanisms of action are obscure. Since 1980 when we and others hypothesized a role of neurotensin (NT) as an endogenous antipsychotic, strong evidence (anatomical, biochemical, pharmacological, and behavioral) has been gathered in our laboratory and others suggesting that mesolimbic NT transmission is involved in both phenomena. Currently the lines of research in the laboratory include manipulation of the mesolimbic NT system (via knock out mice and viral vector technologies), exploration of the interaction between the estrous cycle, schizophrenia and the NT system; and the study of protein-protein interaction between NT and dopamine receptors in vitro and in vivo. In collaboration with Dr. Arnold Mandell and Dr. Karen Selz we have also been investigating how hydrophobic interactions between protein motifs, as identified via mathematical analysis of the primary amino acid sequence, can be used to generate novel biologically active peptides. The techniques currently used in our laboratory range from theoretical design of novel peptides, molecular biology, cellular biology, to genetics, and behavioral pharmacology.
Our lab also studies the pharmacokinetics and pharmacodyanmics of psychotherapeutics. One of the most relevant applications of this has been studies from our lab investigating the effects of fetal and infant exposure to antidepressants and antipsychotics. We are currently assessing the effects of in utero drug exposure on the development of serotonergic and noradrenergic brain systems. Also, in collaboration with Dr. Zachary Stowe and James Ritchie we are able to directly measure drug exposure in infants of breast-feeding mothers which allows us to directly determine mother-infant transmission rates. In addition, we have recently been developing methodologies to assess ex vivo receptor occupancy of antidepressant medications in clinical populations. This may lead to relatively simple methods to correlate pharmacokinetic parameters with treatment response, and also help identify patients who are nonresponders due to inadequate dosing. We have also initiated studies to correlate in vivo receptor occupancy as measured via PET imaging with our new ex vivo methodology.

Bottom Row: L to R Neal Vaishnavi, Feng Yang (Scott), Ricardo Cáceda, David Gutman
Middle Row: Jessica Levin, Tiesha Cassell
Back Row: L to R Michael Owens, Susan Plott, Vani Arcuragi, Catherine Cappello, Vasili Egnatashvili, Amanda Nemeroff, David Knight, Charles Nemeroff
Not pictured: Becky Kinkead

Former graduate students:
Steven Stout, M.D., Ph.D. Focus: CRF and antidepressants
Elisabeth Binder, M.D.,Ph.D. Focus: Neurotensin, dopamine and schizophrenia
Kelly Hartline Skelton, M.D., Ph.D. Focus: CRF and benzodiazepines
Jonathon McConathy, M.D. pending, Ph.D. Focus: PET ligands for the NET and DAT

Former Post-Doctoral and Visiting Fellows:
Yoshitaka Ohkubo, Ph.D.
Hiro Emoto, Ph.D.
Jin He’Han, M.D. University of Seoul
James Radke, Ph.D.
Lotta Arborelius, Ph.D. Karolinski Institute
Osvaldo Gaytan, M.D., Ph.D. Resident in Psychiatry, Emory University
Michelle Gilmor, Ph.D. Shire Pharmaceuticals

Fig 1: Wavelet decomposition of the primary sequence of the human M1 receptor

Below is a sample of some of our more recent publications.

1999

1. Anand KJS, Coskun V, Thrivikraman KV, Nemeroff CB and Plotsky, PM. 1999. Long-term behavioral effects of repetitive pain in neonatal rat pups. Physiol Behav 66:627-637.
2. Arborelius L, Owens, MJ, Plotsky PM and Nemeroff CB. 1999. The role of corticotropin-releasing factor (CRF) in depression and anxiety disorders. J Endocrinol 160:1-12.
3. Ehlers CL, Somes C, Li T-K, Lumeng L, Kinkead B, Owens MJ and Nemeroff CB. 1999. Neurotensin studies in alcohol naive, preferring and non-preferring rats. Neurosci 93:227-236.
4. Nemeroff CB. 1999. The preeminent role of neuropeptide systems in the early pathophysiology of Alzheimer’s disease: up with CRF, down with acetylcholine. Arch Gen Psychiat 56:991-992.
5. Owens MJ and Nemeroff CB. 1999. Corticotropin releasing factor antagonists in affective disorders. Expert Opinions on Investigational Drugs 8:1849-1858.
6. Owens MJ and Nemeroff CB. 1999. Corticotropin-releasing factor antagonists: therapeutic potential in the treatment of affective disorders. CNS Drugs 12:85-92.

Gilmor et al., (2002) Amer J Psych 159:1702-1710
Figure 2: Correlations between serum concentrations with ex vivo occupancy at the serotonin or norepinephrine transporter in depressed patients treated with paroxetine or desipramine.

2000

7. Arborelius L, Skelton KH, Thrivikraman KV, Plotsky PM, Schulz DW and Owens MJ. 2000. Chronic administration of the selective CRF1 receptor antagonist CP-154,526: behavioral, endocrine and neurochemical effects in the rat. J. Pharmacology & Experimental Therapeutics 294:588-597.
8. Bouwer C, Claassen J, Dinan TG and Nemeroff CB. 2000. Prednisone augmentation in treatment-resistant depression with fatigue and hypocortisolemia: a case series. Depression and Anxiety 12:44-50.
9. Coplan JD, Smith ELP, Trost RC, Scharf B, Altemus M, Bjornson L, Owens MJ, Gorman JM, Nemeroff CB and Rosenblum LA. 2000. Growth hormone response to clonidine in adversely reared young adult primates: relationship to serial cerebrospinal fluid corticotropin-releasing factor concentrations. Psychiatry Research 95:93-102.
10. Garlow SJ, Owens MJ, Kelsey J and Nemeroff CB. 2000. Nefazodone. In: Comprehensive Textbook of Psychiatry/VII (BJ Sadock and VA Sadock, Eds.), Lippincott Williams and Wilkins, Baltimore, pp. 2412-2418.
11. Goodman MM, Kilts CD, Keil R, Shi B, Martarello L, Xing D, Votaw J, Ely TD, Lambert P, Owens MJ, Camp VM, Malveaux E and Hoffman JM. 2000. 18F-labeled FECNT: a selective radioligand for PET imaging of brain dopamine transporters. Nuclear Medicine & Biology 27:1-12.
12. Gutman DA, Owens MJ and Nemeroff CB. 2000. Corticotropin-releasing factor antagonists as novel psychotherapeutics. Drugs of the Future 25:923-931.
13. Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, Miller AH and Nemeroff CB. 2000. Pituitary-adrenal and autonomic responses to stress in adult women after sexual and physical abuse in childhood. JAMA 284:592-597.
14. Kaufman J, Plotsky PM, Nemeroff CB and Charney D. 2000. Effects of early adverse experiences on brain structure and function: clinical implications. Biol Psychiat 48:778-790.
15. Keller MB, McCullough JP, Klein DN, Arnow B, Dunner DL, Gelenberg AJ, Markowitz JC, Nemeroff CB, Russell JM, Thase ME, Trivedi MH and Zajecka J. 2000. A comparison of nefazodone, cognitive behavioral analysis system of psychotherapy, and their combination for treatment of chronic depression. New Engl J Med 342:1462-1470.
16. Kinkead B, Binder EB and Nemeroff CB. 2000. Olanzapine and neurotensin. In: Olanzapine (Zyprexa) – A Novel Antipsychotic. (PV Tran, F Bymaster, N Tye, J Herrera, A Breier and G Tollefson, Eds), Lippincott Williams & Wilkins Healthcare, Philadelphia, 197-213.
17. Kinkead B, Lorch SM, Owens MJ and Nemeroff CB. 2000. Sex- and estrous cycle-related differences in the effects of acute antipsychotic drug administration on neurotensin-containing neurons in the rat brain. J. Pharmacology & Experimental Therapeutics 295:205-211.
18. Kinkead B, Owens MJ and Nemeroff CB. 2000. Effects of acute and subchronic administration of typical and atypical antipsychotic drugs on the neurotensin system of the rat brain. J. Pharmacology & Experimental Therapeutics 295:67-73.
19. Kinkead B, Owens MJ and Nemeroff CB. 2000. The effects of acute antipsychotic drug administration on the neurotensin system of the developing rat brain. Brain Research Dev Brain Res 124:1-10.
20. Kinkead B, Shahid S, Owens MJ and Nemeroff CB. 2000. Effects of acute and subchronic administration of typical and atypical antipsychotic drugs on the neurotensin system of the rat brain. J Pharmacol Exp Ther 295:67-73.
21. Kujawa MJ and Nemeroff. 2000. The biology of bipolar disorder. In: Bipolar Disorders: 100 years after manic-depressive insanity, (A Marneros and J Angst, Eds), Kluwer Academic Publishers, Great Britain, 281-314.
22. Ladd CO, Huot RL, Thrivikraman KV, Nemeroff CB, Meaney MJ and Plotsky PM. 2000. Long-term behavioral and neuroendocrine adaptations to adverse early experience. In: The Biological Basis for Mind/Body Interactions. Progress in Brain Research (EA Mayer and C Saper, Eds), Elsevier Press, Amsterdam 122:81 103.
23. Newport DJ and Nemeroff CB. 2000. Neurobiology of posttraumatic stress disorder. Current Opinion in Neurobiology 10:211-218.
24. Musselman DL, Marzec UM, Manatunga A, Penna S, Reemsnyder A. Knight BT, Baron A, Hanson SR and Nemeroff CB. 2000. Platelet reactivity in depressed patients treated with paroxetine: preliminary findings. Arch Gen Psychiat 57:875-882.
25. Musselman DL, McDonald W and Nemeroff CB. 2000. Effects of mood and anxiety disorders on the cardiovascular system. In: Hurst’s The Heart, 10th Edition, (V Fuster, RW Alexander and RA O’Rourke, Eds), McGraw-Hill Publishers, 2227-2250.
26. Nemeroff CB. 2000. Neuroendocrinology. In: New Oxford Textbook of Psychiatry (MG Gelder, JJ Lopez-Ibor and NC Andreasen, Eds), Oxford University Press, New York, New York 1:181-188.
27. Owens MJ, Knight DL and Nemeroff CB. 2000. Paroxetine binding to the rat norepinephrine transporter in vivo. Biological Psychiatry 47:842-845.
28. Owens MJ, Nemeroff CB and Bissette G. 2000. Neuropeptides: biology and regulation. In: Comprehensive Textbook of Psychiatry/VII (BJ Sadock and VA Sadock, Eds.), Lippincott Williams and Wilkins, Baltimore, pp. 60-70.
29. Owens MJ, Nemeroff CB and Knight DL. 2000. Correspondence: Paroxetine binding to the rat norepinephrine transporter in vivo. Biological Psychiatry 48:954-956.
30. Ressler KJ and Nemeroff CB. 2000. The role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depression and Anxiety 12:2-19.
31. Skelton KH, Nemeroff CB and Owens MJ. 2000. A comparison of plasma alprazolam concentrations following different routes of chronic administration in the Sprague-Dawley rat: implications for psychotropic drug research. Psychopharmacology 151:72-76.
32. Skelton KH, Nemeroff CB, Knight DL and Owens MJ. 2000. Chronic administration of the triazolobenzodiazepine alprazolam: bioavailability and opposite regulation of corticotropin-releasing factor and urocortin systems. J. Neuroscience 20:1240-1248.
33. Skelton KH, Owens MJ and Nemeroff CB. 2000. The neurobiology of urocortin. Regulatory Peptides 93:85-92.
34. Stout SC, Mortas P, Owens MJ, Nemeroff CB and Moreau J-L. 2000. Increased corticotropin-releasing factor concentrations in the bed nucleus of the stria terminalis of anhedonic rats. European J. Pharmacology 401:39-46.
35. Stowe ZN, Cohen LS, Hostetter A, Ritchie JC, Owens MJ and Nemeroff CB. 2000. Paroxetine in human breast milk and nursing infants. American Journal of Psychiatry 157:185-189.
36. Vythilingam M, Anderson GM, Owens MJ, Halaszynski TM, Bremner JD, Carpenter LL, Heninger GR, Nemeroff CB and Charney DS. 2000. Cerebrospinal fluid corticotropin-releasing hormone (CRH) in healthy human: effects of yohimbine and naloxone. J. Clinical Endocrinology & Metabolism 85:4138-4145.
37. Xing D, Chen P, Keil R, Kilts CD, Shi B, Camp VM, Malveaux G, Ely T, Owens MJ, Votaw J, Davis M, Hoffman JM, BaKay RAE, Subramanian T, Watts RL and Goodman MM. 2000. Synthesis, biodistribution, and primate imaging of fluorine-18 labeled 2b-carbo-1'-fluoro-2-propoxy-3b-(4-chlorophenyl)tropanes: ligands for the imaging of dopamine transporters by positron emission tomography. J. Medicinal Chemistry 43:639-648.

Gilmor et al., (2002) Amer J Psych 159:1702-1710

Figure 3: Model of the dynamics of free/protein bound drug concentrations in CSF and serum and in vivo occupancy at a generic transporter protein

2001

38. Binder E, Kinkead B, Owens MJ and Nemeroff CB. 2001. Neurotensin and dopamine interactions. Pharmacological Reviews 53:453-486.
39. Binder E, Kinkead B, Owens MJ, Kilts CD and Nemeroff CB. 2001. Enhanced neurotensin neurotransmission is involved in the clinically relevant behavioral effects of antipsychotic drugs: evidence from animal models of sensorimotor gating. J Neuroscience 21:601-608.
40. Binder EB, Kinkead B and Nemeroff CB. 2001. Neuropeptides. In: Current Issues in the Psychopharmacology of Schizophrenia, (A Brier, PV Tran, J Herrera, F Bymaster, G Tollefson, Eds), Lippincott Williams & Wilkins, Baltimore MD, 349-371.
41. Binder EB, Kinkead B, Owens MJ and Nemeroff CB. 2001. Neurotensin and dopamine interactions. Pharmacol Rev 53:453-486.
42. Binder EB, Kinkead B, Owens MJ and Nemeroff CB. 2001. The role of neurotensin in the pathophysiology of schizophrenia and the mechanism of action of antipsychotic drugs. Biological Psychiatry 50:856-872.
43. Binder EB, Kinkead B, Owens MJ, Kilts CD and Nemeroff CB. 2001. Enhanced neurotensin neurotransmission is involved in the clinically relevant behavioral effects of antipsychotic drugs: evidence from animal models of sensorimotor gating. J Neurosci 21:601-608.
44. Coplan JD, Smith ELP, Altemus M, Scharf BA, Owens MJ, Nemeroff CB, Gorman JM and Rosenblum LA. 2001. Variable foraging demand rearing: sustained elevations in cisternal cerebrospinal fluid corticotropin-releasing factor concentrations in adult primates. Biological Psychiatry 50:200-204.
45. Stowe ZN, Cohen LS, Ritchie JC, Owens MJ and Nemeroff CB. 2001. Letters to the editor. American Journal of Psychiatry 158:144-145.
46. Stout SC, Owens MJ and Nemeroff CB. 2001. Neurokinin1 receptor antagonists as potential antidepressants. Annual Reviews in Pharmacology & Toxicology 41:877-906.
47. Owens MJ, Knight BS and Nemeroff CB. 2001. Second generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biological Psychiatry 50:345-350.
48. Charney DS, Coyle JT, Davis KL and Nemeroff CB, Eds.. 2001. Neuropsychopharmacology: The Fifth Generation of Progress, Lippincott
49. Gutman DA, Owens MJ and Nemeroff CB. 2001. CRF receptor antagonists: a new approach to the treatment of depression. Pharmaceutical News 8:18-25.
50. Heim C and Nemeroff CB. 2001. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiat 49:1023-1039.
51. Heim C, Newport DJ, Bonsall R, Miller AH and Nemeroff CB. 2001. Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiat 158:575-581.
52. Mandell AJ, Selz KA, Owens MJ, Shlesinger MF, Gutman DA and Arcuragi V. 2001. Hydrophobic mode-targeted, algorithmically designed peptide ligands as modulators of protein thermodynamic structure and function. In: Drug-Receptor Thermodynamics: Introduction and Applications (RB Raffa, ed.), John Wiley & Sons, New York, pp. 655-700.
53. Martarello L, Kilts CD, Ely T, Owens MJ, Nemeroff CB, Camp M and Goodman MM. 2001. Synthesis and characterization of fluorinated and iodinated pyrrolopyrimidines as PET/SPECT ligands for the CRF1 receptor. Nuclear Medicine and Biology 28:187-195.
54. Musselman DL, Miller AH, Porter MR, Manatunga A, Gao F, Penna S, Pearce BD, Landry J, Glover S, McDaniel JS and Nemeroff CB. 2001. Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiat 158:1252-1257.
55. Musselman DL, Lawson DH, Gumnick JF, Manatunga A, Penna S, Goodkin R, Greiner K, Nemeroff CB and Miller AH. 2001. Paroxetine for the prevention of depression induced by high dose interferon-alpha. New Engl J Med 344:961-966.
56. Newport DJ and Nemeroff CB. 2001. Hypothalamic-pituitary-adrenal axis: normal physiology and disturbances in depression. In: Physical Consequences of Depression (J Thakore, Ed), Wrightson Biomedical Publishing, Ltd, Great Britain, 1-22.
57. Nemeroff CB. 2001. Progress in the Battle with the Black Dog: Advances in the Treatment of Depression. Editorial, Am J Psychiat 158:1555-1557.
58. Nemeroff CB and Owens MJ. 2001. Contribution of modern neuroscience to developing new treatments for psychiatric disorders in the 21st century. In: Treatment of Depression: Bridging the 21st Century (MM Weissman, ed.), American Psychiatric Press, Washington DC, pp 61-81.
59. O’Brien D, Skelton KH, Owens MJ and Nemeroff CB. 2001. Are CRF receptor antagonists potential antidepressants? Human Psychopharmacology 16:81-87.
60. Owens MJ and Nemeroff CB. 2001. An old transmitter in a new millennium. CNS Spectrums 6:655.
61. Owens MJ and Risch SC. 2001. Atypical antipsychotics. In: Essentials of Clinical Psychopharmacology (AF Schatzberg and CB Nemeroff, Eds.), American Psychiatric Association Press, Washington, DC, pp 125-154.
62. Radke JM, Owens MJ and Nemeroff CB. 2001. The effects of glutamate receptor agonists on neurotensin release using in vivo microdialysis. Eur J Pharmacol 411:129-134.
63. Ressler KJ and Nemeroff CB. 2001. Role of norepinephrine in the pathophysiology of neuropsychiatric disorders. CNS Spectrums 6:663-670.
64. Ressler KJ and Nemeroff CB. 2001. Peptides and psychiatry. In: International Encyclopedia of the Social & Behavioral Sciences (NJ Smelser and PB Baltes, Eds), Pergamon, Oxford, 11189-11195.
65. Stout SC, Owens MJ, Lindsey KP, Knight DL and Nemeroff CB. 2001. Effects of sodium valproate on corticotropin-releasing factor systems in rat brain. Neuropsychopharmacology 24:624-631.


Mathew et al., (2002) Stress 5:185-193.
Figure 5: Early adverse rearing can cause persistent changes in CSF CRF concentrations in young adult rhesus macaques

Year 2002

66. Arborelius L and Nemeroff CB. 2002. Preclinical models of anxiety. In: Textbook of Anxiety, D Stein and E Hollander, Eds, American Psychiatric Publishing, 29-42.
67. Binder EB, Gross RE, Nemeroff CB and Kilts CD. 2002. Effects of neurotensin receptor antagonism on latent inhibition in Sprague-Dawley rats. Psychopharmacol 161:288-295.
68. Boswell EB, Anfinson TJ and Nemeroff CB. 2002. Neuropsychiatric aspects of endocrine disorders. In: Textbook of Neuropsychiatry, 4th Edition (S. Yudofsky and R Hales, Eds.), American Psychiatric Association Press, Inc. Washington, DC, 851-875.
69. Cummins TK, Anand KJS and Nemeroff CB. 2002. Developmental psychoneuroendocrinology. In: Child and Adolescent Psychiatry: A Comprehensive Textbook, 3rd Edition, (M Lewis, Ed), Lippincott Williams & Wilkins, Baltimore, 93-119.
70. Gilmor M, Owens MJ and Nemeroff CB. 2002. Inhibition of the norepinephrine transporter in depressed patients treated with paroxetine. American Journal of Psychiatry 159:1702-1710.
71. Gutman DA and Nemeroff CB. 2002. Neurobiology of early life stress: rodent studies. Seminars in Clinical Neuropsychiatry 7:89-95.
72. Gutman DA and Nemeroff CB. 2002. Neuroendocrinology. In: Biological Psychiatry, (H D’haenen, JA den Boer and P Willner, Eds), John Wiley & Sons, 97-110.
73. Gutman DA, Musselman DL and Nemeroff CB. 2002. Neuropeptide alterations in depression and anxiety disorders. In: Handbook of Depression and Anxiety: A Biological Approach, (JA denBoer, JM AdSitsen and S Kasper, eds), Marcel Dekker, Inc. (in press).
74. Nemeroff CB and Gutman DA. 2002. Neuroendocrinological research in psychiatry. In: Psychiatry as a Neuroscience, (JJ Lopez Ibor, W Gaebel, M Maj and N Sartorius, Eds) John Wiley & Sons 91-124.
75. Hamid EH, Hyde TM, Egan MF, Wolf SS, Herman MM, Nemeroff CB and Kleinman JE. 2002. Neurotensin receptor binding abnormalities in the entorhinal cortex in schizophrenia and affective disorders. Biol Psychiat 51:795-800.
76. Heim C and Nemeroff CB. 2002. Neurobiology of early life stress: clinical studies. Seminars in Clin. Neuropsychiat 7:147-159.
77. Heim C and Nemeroff CB. 2002. Neurobiology of early-life stress and its disorders. In: Textbook of Pediatric Psychopharmacology (A Martin, L Scahill, D Charney and JF Leckman, Eds), Oxford University Press 110-124.
78. Heim C, Newport DJ, Wagner D, Wilcox MS, Miller AH and Nemeroff CB. 2002. The role of early adverse experience and adulthood stress in the prediction of neuroendocrine stress reactivity in women: a multiple regression analysis. Depression & Anxiety 15:117-125.
79. Kinkead B and Nemeroff CB. 2002. Neurotensin: an endogenous antipsychotic? Current Opinion in Pharmacology 2:99-103.
80. Mathew SJ, Coplan JD, Smith ELP, Scharf BA, Owens MJ, Nemeroff CB, Mann JJ, Gorman JM and Rosenblum LA. 2002. Cerebrospinal fluid concentrations of biogenic amines and corticotropin-releasing factor in adolescent primates as a function of timing of adverse early rearing. Stress 5:185-193.
81. Musselman DL, Marzec U, Davidoff M, Manatunga AM, Gao F, Reemsnyder A, Duggirala S, Larsen H, Taylor RW, Hanson and Nemeroff CB. 2002. Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatment. Depression and Anxiety 15:91-101.
82. Nemeroff CB and Owens MJ. 2002. Treatment of mood disorders. Nature Neuroscience 5(suppl):1068-1070.
83. Nemeroff CB and Putnam JS. 2002. Anticholinergics and amantadine. In: Comprehensive Textbook of Psychiatry, VIII Edition (B Sadock and V Sadock , eds), Lipppincott, Williams & Wilkins (in press).
84. Nemeroff CB. 2002. Comorbidity of mood and anxiety disorders: the rule, not the exception? Editorial, Am J Psychiat 159:1.
85. Nemeroff CB. 2002. Recent advances in the neurobiology of depression. Psychopharmacol Bull 36:6-23.
86. Newport DJ and Nemeroff CB. 2002. Stress. In: Encyclopedia of the Human Brain (VS Ramachandran, Ed), Elsevier Science, Vol. 4, pp 449-462.
87. Newport DJ, Stowe ZN and Nemeroff CB. 2002. Parental depression: animal models of an adverse life event. Am J Psychiat 159:1265-1283.
88. Owens MJ and Rosenbaum JF. 2002. Escitalopram: a second generation SSRI. CNS Spectrums 7(4S1):34-39, 2002.
89. Ressler KJ and Nemeroff CB. 2002. Depression. In: The Molecular and Genetic Basis of Neurologic and Psychiatric Disease, 3rd edition. (RN Rosenberg, SB Prusiner, S DiMauro, RL Barchi and EJ Nestler, eds), (in press).
90. Rosenblum LA, Smith ELP, Altemus M, Scharf BA, Owens MJ, Nemeroff CB, Gorman JM and Coplan JD. 2002. Differing concentrations of corticotropin-releasing factor and oxytocin in the cerebrospinal fluid of bonnet and pigtail macaques. Psychoneuroendocrinology 27:651-660.
91. Schatzberg AF, Garlow SJ and Nemeroff CB. 2002. Molecular and cellular mechanisms in depression. In: Neuropsychopharmacology, The Fifth Generation of Progress (DS Charney, JT Coyle, KL Davis and CB Nemeroff, Eds), 1039-1050.
92. Stout SC, Owens MJ and Nemeroff CB. 2002. Regulation of CRF gene expression and peptide concentrations by stress and chronic antidepressant treatment. J. Pharmacology & Experimental Therapeutics 300:1085-1092.
93. Stout SC, Owens MJ and Nemeroff CB. 2002. Response to letter to the editor. Neuropsychopharmacology 26:413-414.
94. Vythilingam M, Heim C, Newport DJ, Miller AH, Anderson E, Vermetten E, Bronen R, Staib L, Charney DS, Nemeroff CB and Bremner JD. 2002. Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiat 159:2072-2080.

Binder et al., (2001) J Neuroscience 21(2) 601-608

Figure 6: Interactions of neurotensin with the dopamine mesolimbic system in relationship to the pathophysiology of schizophrenia

2003

95. Arborelius L, Plotsky, PM, Nemeroff CB and Owens MJ. 2003. Increased reponsiveness of 5-HT cell firing to citalopram in adult rats previously subjected to maternal deprivation. Neuropharmacology (submitted).
96. Caceda R. Kinkead B. Nemeroff CB. Do neurotensin receptor agonists represent a novel class of antipsychotic drugs? Seminars in Clinical Neuropsychiatry. 8(2):94-108, 2003.
97. Compton MT and Nemeroff CB. 2003. Depression and bipolar mood disorder. In: Scientific American Medicine (in press).
98. Marcin MS and Nemeroff CB. 2003. The neurobiology of social phobia: the relevance of fear and anxiety. Acta Psychiat Scand (in press).
99. Stowe ZN, Hostetter A, Owens MJ, Ritchie JC, Sternberg K, Cohen LS and Nemeroff CB. 2003. The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations. J. Clinical Psychiatry 64:73-80.
100. Ritchie JC, Davis TP and Nemeroff CB. 2003. Action of three ectopeptidases on corticotropin-releasing factor: metabolism and functional aspects. Neuropsychopharmacol 28:22-33.
101. Purselle DC and Nemeroff CB. 2003. The serotonin transporter: a potential substrate in the biology of suicide. Neuropsychopharmacol 28:613-619.
102. Nemeroff CB. 2003. Anxiolytics: past, present, and future agents. J Clin Psychiat 64:3-6.
103. Owens MJ and Nemeroff CB. 2003. Neuropharmacology of paroxetine. Psychopharmacology Bulletin 37(S1):8-18.
104. Owens MJ and Nemeroff CB. 2003. Neuropharmacology of valproic acid. Psychopharmacology Bulletin (in press).
105. Newport DJ, Heim C, Owens MJ, Ritchie JC, Ramsey C, Bonsall R, Miller AH and Nemeroff CB. 2003. Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test: a multiple regression analysis. Neuropsychopharmacol 28:569-576.
106. Newport DJ, Heim C, Owens MJ, Ritchie JC, Ramsey CH, Bonsall R, Miller AH and Nemeroff CB. 2003. Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test: a multiple regression analysis. Neuropsychopharmacology 28:569-576.
107. Owens MJ and Ritchie JC. 2003. Clinical neurochemistry. In: Neurobiology of Mental Illness, 2nd edition (DS Charney, EJ Nestler and BS Bunney, Eds.), Oxford University Press, New York, (in press).
108. Gilmor ML, Skelton KH, Nemeroff CB and Owens MJ. 2003. The effects of chronic treatment with the mood stabilizers valproic acid and lithium on corticotropin-releasing factor neuronal systems. J. Pharmacology & Experimental Therapeutics 305:434-439.
109. Goodman MM, Chen P, Plisson C, Martarello L, Galt J, Votaw JR, Kilts CD, Malveux G, Camp VM, Shi B, Ely TD, Howell H, McConathy J and Nemeroff CB. 2003. Synthesis and characterization of iodine-123 labeled 2ß-carbomethoxy-3ß-(4-((Z)-2-iodoethenyl)phenyl)nortropane. A ligand for in vivo imaging of serotonin transporters by single-photon-emission tomography. J Med Chem 46:925-935.
110. Gutman DA, Owens MJ and Nemeroff CB. 2003. The CRF1 receptor antagonist, R121919, blocks endocrine and behavioral responses to stress. J. Pharmacology & Experimental Therapeutics 304:874-880.
111. Heim C, Meinlschmidt G and Nemeroff CB. 2003. The neurobiology of early-life stress and its relationship to PTSD. Psychiatric Annals 33:18-26
112. Kinkead B and Nemeroff CB. 2003. Neurotensin. In: Encyclopedia of Neuroscience, 3rd Edition (G Adelman and BH Smith, Eds), Elsevier Press (in press).
113. Mandell AJ, Selz KA, Owens MJ and Shlesinger MF. 2003. Broomhead-King hydrophobic modes in receptor-targeted peptide design: how to find modes in a short data sequence. In: Unsolved Problems of Noise (L Kish and S Bezrukov, eds), Am. Inst. Physics Press, College Park MD, (in press).
114. Mandell AJ, Selz KA, Owens MJ, Kinkead B, Shlesinger MF, Gutman DA and Arcuragi V. 2003. Cellular and behavioral effects of the D2 dopamine receptor hydrophobic eigenmode-targeted peptide ligands. Neuropsychopharmacology 2003 Jul;28 Suppl 1:S98-107.
115. McConathy J and Owens MJ. 2003. Stereochemistry and drug action. J. Clinical Psychiatry – Primary Care Companion (in press).
116. McConathy J, Nemeroff CB and Owens MJ. 2003. Chiral antidepressants: single enantiomers versus mixtures of enantiomers. Essential Psychopharmacology (in press).
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Figure 7: Latent inhibition is a classical test used to detect antipsychotic drugs. This study suggests that NT is required for the normal expression of LI.

Figure 8: This study demonstrate alprazolam, a commonly prescribed anxiolytic drug, may directly interact with the CRF2 receptor system

Figure 9: 7 day treatment with the CRF1 receptor antagonist R121919 dose dependently blocks cortical CRF1 receptor binding, without affecting CRF2 receptor binding in the lateral septum.