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Charles V. Vorhees, PhD

Title

Professor / Principal Investigator

Appointment

Professor of Pediatrics; Professor of Environmental Health

Email

charles.vorhees@cchmc.org

Phone

513-636-8622

Fax

513-636-3912

Bio

Dr. Vorhees has served on numerous National Institutes of Health site visit committees, special emphasis panels, and ad hoc review committees since 1984, and was a regular member of a study section from 1994-1998, serving as interim chair in 1997. He has also reviewed grant applications for the National Science Foundation, Veterans Administration, Wellcome Trust, March of Dimes, and other agencies. He has served on advisory committees to the US Food and Drug Administration, US Environmental Protection agency, National Research Council, several private foundations, and a number of pharmaceutical companies.

Dr. Vorhees was Director of the Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, 1998-2004.

Credentials

MA: Neurobiology Program, Vanderbilt University, Nashville, TN, 1973.

PhD: Neurobiology Program, Vanderbilt University, Nashville, RN, 1976.

Position History

Charles V. Vorhees, PhD, Vanderbilt University, Neurobiology Program
Postdoctoral Research Scholar, Neurotoxicology and Teratology, Cincinnati Children's Research Foundation, 1976-1978
Assistant Professor of Pediatrics, 1978-1982
Associate Professor (tenured), 1982-1988
Professor of Pediatrics and Environmental Health, 1988-present

Awards and Honors

National Institute of Mental Health Predoctoral fellowship
Eli Lilly Distinguished Lecturer, 1990
Member, Neurophysiology and Neuroanatomy Study Section, National Institutes of Health, 1994-1998
Member, Reproductive and Developmental Toxicology Committee, National Research Council of the National Academy of Science, 1997-2000

Research

Visit Dr. Vorhees' Lab Site.

Effects of amphetamines on brain development, behavior, and neurotoxicity; neurobiological substrates of learning and memory; proteins for neurotransmitter receptors, second messenger transduction, and regulators of signaling pathways.

Dr. Charles Vorhees' lab is pursuing two lines of research. One is on the prenatal effects of stimulant drugs of abuse on brain development and later learning and memory function. Dr. Vorhees' lab is the first to report that late, but not early, neonatal exposure to methamphetamine in rats (a period of brain development analogous to human third trimester) results in impaired spatial learning and memory, while sparing sequential and other forms of learning. This treatment also increases corticosterone dramatically. This was surprising because the effect occurs during the adrenocortical Stress HypoResponsive Period (or SHRP) stage of development.

Given this, the lab is examining methamphetamine treated offspring for the detailed pattern of how methamphetamine increases corticosterone at different developmental ages and what the effect is of single versus multiple doses. More recently, the findings with methamphetamine on learning have been extended to related substituted amphetamines, including ecstasy (MDMA) and fenfluramine. The lab has found that these drugs not only induce spatial learning and memory deficits similar to those seen with methamphetamine, they also induce impairments of sequential learning. Together, the data reveal previously unrecognized effects resulting from intrauterine exposure to substituted amphetamines and raise issues over the safety of dopaminergic and serotonergic-acting drugs on long-term brain development.

The second line of research uses gene targeting to disrupt genes whose protein products may be involved in learning and memory. The lab has created a knockout mouse with the calcium calmodulin phophodiesterase B1 gene disrupted (CAM PDE). Recent studies have shown that homozygotic mutants for this PDE (PDE1B) show no overt abnormalities, however, when assessed for spatial learning, they exhibit impaired learning. They also show changes in performance that vary as a function of the stimulus characteristic of the cues needed for successful spatial recall. The lab has also shown that mice with disruption of the DFF-45 gene, a recently identified gene involved in apoptosis and disrupted by Dr. Ming Xu, exhibit enhanced learning and memory. The lab is also behaviorally phenotyping other knockout mice in which genes expressed predominately in the brain are disrupted as part of a larger effort to understand the biological basis of learning and memory.

Research Grants and Contracts

2005 - 2010
National Institutes of Health, Developmental Effects of Methamphetamine-like Stimulants: Vorhees C (PI)
2006 - 2011
National Institutes of Health, Effects of Neonatal MDMA on Brain and Behavior: Vorhees C (PI)

Publications, Most Recent

Vorhees CV, Reed TM, Morford LL, Fukumura M, Wood SL, Brown CA, Skelton MR, McCrea AE, Rock SL, Williams MT. (2005) Periadolescent rats (P41-50) exhibit increased susceptibility to D-methamphetamine-induced long-term spatial and sequential learning deficits compared to juvenile (P21-30 or P31-40) or adult rats (P51-60). Neurotoxicol Teratol 27:117-34.
Lanphear BP, Vorhees CV, Bellinger DC. (2005) Protecting children from environmental toxins. PLoS Med 2:e61.
Williams MT, Schaefer TL, Ehrman LA, Able JA, Gudelsky GA, Sah R, Vorhees CV. (2005) 3,4-Methylenedioxymethamphetamine administration on postnatal day 11 in rats increases pituitary-adrenal output and reduces striatal and hippocampal serotonin without altering SERT activity. Brain Res 1039:97-107.
Broening HW, Morford LL, Vorhees CV. (2005) Interactions of dopamine D1 and D2 receptor antagonists with D-methamphetamine-induced hyperthermia and striatal dopamine and serotonin reductions. Synapse 56:84-93.
Brunskill EW, Ehrman LA, Williams MT, Klanke J, Hammer D, Schaefer TL, Sah R, Dorn GW, 2nd, Potter SS, Vorhees CV. (2005) Abnormal neurodevelopment, neurosignaling and behaviour in Npas3-deficient mice. Eur J Neurosci 22:1265-76.
Cohen MA, Skelton MR, Schaefer TL, Gudelsky GA, Vorhees CV, Williams MT. (2005) Learning and memory after neonatal exposure to 3,4-methylenedioxymethamphetamine (ecstasy) in rats: interaction with exposure in adulthood. Synapse 57:148-59.
Curran CP, Miller KA, Dalton TP, Vorhees CV, Miller ML, Shertzer HG, Nebert DW. (2006) Genetic differences in lethality of newborn mice treated in utero with coplanar versus non-coplanar hexabromobiphenyl. Toxicol Sci 89:454-64.
Able JA, Gudelsky GA, Vorhees CV, Williams MT. (2006) 3,4-Methylenedioxymethamphetamine in adult rats produces deficits in path integration and spatial reference memory. Biol Psychiatry 59:1219-26.
Crawford CA, Williams MT, Kohutek JL, Choi FY, Yoshida ST, McDougall SA, Vorhees CV. (2006) Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPgammaS binding in adult rats. Brain Res 1077:178-86.
Ehrman LA, Williams MT, Schaefer TL, Gudelsky GA, Reed TM, Fienberg AA, Greengard P, Vorhees CV. (2006). Phosphodiesterase 1B modulates the effects of methamphetamine on locomotor activity and spatial learning through a DARPP-32-dependent pathway: Evidence from PDE1B-DARPP32 double-knockout mice. Genes Brain Behav., (In press).
Adami F, Liao G, Morozov YM, Schloemer A, Schmithrost VJ, Lorenz JN, Dunn RS, Vorhees CV, Wills-Karp M, Degen JL, Davis RJ, Mizushima N, Rakic P, Darzinski BJ, Holland SK, Sharp FR, Kuan CY. (2006). Cerebral ischemia-hypoxia induces reperfusion deficits and autophagy. Am. J. Pathol., (In press).
Schaefer TL, Ehrman LA, Gudelsky GA, Vorhees CV, Williams MT. (2006). A comparison of monoamine and corticosterone levels 24 hours following +methamphetamine, ±3,4-methylenedioxymethamphetamine, cocaine, ±fenfluramine, or ±methylphenidate administration in the neonatal rat. J. Neurochem., (In press).
Williams MT, Herring NR, Schaefer TL, Skelton MR, Campbell NG, Lipton JW, McCrea AE, Vorhees CV. (2006). Alterations in body temperature, corticosterone, and behavior following the administration of 5-methoxy-diisopropyltryptamine ('Foxy') to adult rats: A new drug of abuse. Neuropsychopharmacology, (Provisionally accepted pending minor revision).
Williams MT, Schaefer TL, Furay AR, Ehrman LA, Vorhees CV. (2006). Ontogeny of the adrenal response to (+)-methamphetamine in neonatal rats: the effect of prior drug exposure. Stress, (In press).
Skelton MR, Williams MT, Vorhees CV. (2006). Treatment with MDMA from P11-20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats. Psychopharmacology, (Provisionally accepted).
Vorhees CV, Williams MT. (2006). Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nature Protocols, 1, (In press).

Professional Organization Memberships

Teratology Society, 1977-present
Neurobehavioral Teratology Society, 1977-present
American Association for the Advancement of Science, 1980-present
Society for Neuroscience, 1984-present
International Brain Research Organization, 1984-present
Society of Toxicology, 1990-present

Special Interests

Effects of prenatal exposure to chemicals on brain development and cognitive function in the offspring.

Editing

Editor-in-Chief, Neurotoxicology and Teratology, 1996-2005.
Section Editor for Developmental Neurotoxicology, Neurotoxicology and Teratology, 1996-2005.