Emory University School of Medicine
Department of Psychiatry & Behavioral Sciences
Laboratory of Neuropsychopharmacology
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Corticotropin-Releasing Factor (CRF) Studies:
CRF Expression: Physical drug withdrawal produces a profound increase in CRF expression within the cortex. These are probably GABAergic interneurons. Skelton et al. 2004.
CRF and Drug Withdrawal: A CRF 1 antagonist attenuates CRF gene expression following benzodiazepine or opiate drug withdrawal.
R121919 & CRF binding: R121919 does not bind to the CRF 2A receptor in vivo.
CRF 2A Eigenmode: Design of CRF 2A receptor-targeted hydrophobic eigenmode matched peptides as functional modulators.
CRF and Early Life Stress: Early life stress may represent thee reason why many depressed subjects have elevated CSF CRF concentrations.
CRF System & Early Life Stress: The first study to demonstrate that early life stress results in persistent changes in the CRF system that last through adulthood. Charlotte Ladd, M.D., Ph.D. performed this study as an Emory undergraduate student.
CRF System & Early Life Stress: The first study to demonstrate that early life stress results in persistent changes in the CRF system in non-human primates. These alterations are still apparent in the same animals (bonnet macaques) now 5-7 years of age. Coplan et al. 1996. Proc Natl Acad Sci USA 93:1619-1623.
CRF Receptor Binding in Suicide Victims: Down-regulated CRF receptors (lower B MAX) in the frontal cortex of a large number or suicide victims. Hypothesized to be the result of chronic CRF hypersecretion.
Comparison of CRF concentrations: Nine out of eleven studies show that depressed subjects exhibited higher average cerebrospinal fluid concentrations of CRF compared to normals. The concentrations decrease during antidepressant therapy.
Corticotropin-Releasing Factor Concentration in the LC: The antixiety drug alprazolam dose-dependently decreases CRF concentration in the LC. The anxiety-provoking drug FG7142 appears to produce opposite effects. Skelton et al. 2000 J Neuroscience 20:1240-1248.
Alprazolam: Chronic alprazolam administration increases measures of function of the CRF 2 system. We hypothesized that the CRF 1 and CRF 2 systems may be “anti-parallel”. Benzodiazepines such as alprazolam may decrease acute stress responses while augmenting stress-coping responses.
Neurotensin (NT) & Neurotensin Receptors (NTR):
Neurotensin Receptor (NTR) Antagonist Blocks Antipsychotic-Induced Enhancement of Latent Inhibition: Latent inhibition is a classic test used to detect antipsychotic drugs. This study suggests that neurotensin (NT) is required for the normal expression of latent inhibition (LI). From Binder et al. 2001. J Neuroscience 21:601-608.
Norepinephrine Transporter (NET):
Antidepressants & Norepinephrine Transporter: Affinity of antidepressants for the human norepinephrine transporter (NET). Owens et al. 1997. JPET 283:1305-1322.
Antidepressant and/or Antipsychotic Occupancy and Fetal Exposure:
Citalopram: In vitro studies in our lab confirmed the serotonin transporter selectivity of the Emory-developed neuroimaging agent ZIENT.
Desipramine Antidepressant: A non-transporter, non-cell surface receptor mediated action of the antidepressant desipramine.
Paroxetine: Correlation between serum concentrations and estimates of ex vivo occupancy at the serotonin or norepinephrine transporter in depressed patients treated with paroxetine or desipramine. Gilmor et al., 2002 American J Psychiatry 159:1702-1710.
Paroxetine and Desipramine: Correlation between serum concentrations and estimates of ex vivo occupancy at the serotonin or norepinephrine transporter in depressed patients treated with paroxetine or desipramine. Gilmor et al., 2002 American J Psychiatry 159:1702-1710.
DNA Microarray: DNA microarray study examining transcripts in the rat brain that are altered by antipsychotic (Haloperidol) drug administration.
Sertraline & SERT Occupancy: In utero exposure to an antidepressant results in similar brain SERT occupancy in pregnant rats and their offspring at delivery.
Fig 1: Wavelet decomposition of the primary sequence of the human M1 receptor
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
