Neurology

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.

Related Links:

• Visit the Vorhees Lab Site

• Visit the Animal Behavioral Core Site

Credentials

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

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

Position History

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
Grass Foundation Lecturer, 2002
Member, Reproductive and Developmental Toxicology Committee, National Research Council of the National Academy of Science, 1997-2000
Member, Neurophysiology and Neuroanatomy Study Section, National Institutes of Health, 1994-1998
Eli Lilly Distinguished Lecturer, 1990

Research

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 path integration 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 also investigates knockout mice that target other genes, including the creatine transporter, saposin and presaposin, Pde4d, Lphn3, Angiotensinogen, and MAP2. The lab has recently begun studying the adult cognitive effects of methamphetamine and the prenatal effects of maternal infection/immune responses on offspring brain development and behavior as models of the prenatal origins of autism and schizophrenia. We collaborate with investigators on animal model of maternal smoking, ADHD, and Na,K-ATPase isoforms, Pten, and are working on new models of the interaction of early exposure to lead, manganese and stress as interacting factors that in combination compromise later cognitive development. Experiments elucidating brain regions involved in path integration (egocentric) versus spatial mapping (allocentric) learning are new areas of research. We also collaborate on the role of the Ah receptor and CYP1a2 in mediating opposing functions of prenatal PCB effects on offspring learning and memory.

Research Grants and Contracts

2007 - 2012 National Institutes of Health, Training Grant in Teratology: Vorhees C (PI)
2007 - 2009 National Institutes of Health, Genetic Differences in PCB-Induced Behavior: Vorhees C and Nebert D (Co-PIs)
2006 - 2011 National Institutes of Health, Effects of Lead, Manganese and Stress During Development: Williams, M (PI), Vorhees (Co-investigator)
2006 - 2011
National Institutes of Health, Effects of Neonatal MDMA on Brain and Behavior: Vorhees C (PI)
2005 - 2010
National Institutes of Health, Developmental Effects of Methamphetamine-like Stimulants: Vorhees C (PI)

Publications, Most Recent

Find more publications by Dr. Vorhees through PubMed.

Skelton, MR, Schaefer, TL, Herring, NR, Grace, CE, Vorhees, CV, Williams, MT (2009). Comparison of the developmental effects of 5-methoxy-N,N-diisopropyltryptamine (Foxy) to (±)-3,4,-methylenedioxymethamphetamine (Ecstasy) in Rats. Psychopharmacology, (In press).
Vorhees, CV, Schaefer, TL, Skelton, MR, Grace, CE, Herring, NR, Williams, MT (2009). ±3,4-Methylenedioxymethamphetamine (MDMA) dose-dependently impairs spatial learning in the Morris water maze after exposure of rats to different five-day intervals from birth to postnatal day 20. Dev. Neurosci., (In press).
Vorhees, CV, Skelton, MR, Grace, CR, Schaefer, TL, Graham, DL, Braun, AA, Williams, MT (2009). Effects of (+)-methamphetamine on path integration and spatial learning, but not locomotor activity or acoustic startle, align with the stress hyporesponsive period in rats. Int. J. Dev. Neurosci., 27: 289-298.
Vorhees, CV, Johnson, HL, Burns, LN, Williams, MT (2009). Developmental treatment with the dopamine D2/3 agonist quinpirole selectively impairs spatial learning in the Morris water maze. Neurotoxicol. Teratol., 31: 1-10.
Loepke, AW, Istaphanous, GK, Miles, L, Hughes, EH, McCann, JC, Kurth, CD, Williams, MT, Vorhees, CV, Danzer, SC (2009). Effects of neonatal anesthesia on neuronal structure and adult neurocognitive function in mice. Anes. Analges., 108: 90-104.
Skelton, MR, Able, JA, Grace, CE, Herring, NR, Schaefer, TL, Gudelsky, GA, Vorhees, CV, Williams, MT (2008). (±)-3,4-methylenedioxymethamphetamine treatment in adult rats impairs path integration learning: A comparison of single versus once per week treatment for five weeks. Neuropharmacology, 55: 1121-1130.
Herring, NR, Schaefer, TL, Gudelsky, GA, Vorhees, CV, Williams, MT (2008). Effect of (+)-Methamphetamine on path integration, novel object recognition, and neurotoxicity in rats. Psychopharmacology, 199: 637-650.
Sun, Y, Jia, L, Williams, MT, Zamzow, M, Ran, H, Quinn, B, Aronow, BJ, Vorhees, CV, Witte, DP Grabowski, GA (2008). Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice. BMC Neurosci., 9: 76.
Sun, Y, Witte, DP, Ran, H, Zamzow, M, Barnes, S, Cheng, H, Han, X, Williams, MT, Skelton, MR, Vorhees, CV, Grabowski, GA (2008). Neurological deficits and glycosphingolipid accumulation in Saposin B deficient mice. Human Mol. Genet., 17: 2345-2356.
Vorhees, CV, Herring, NR, Schaefer, TL, Grace, CE, Skelton, MR, Johnson, HL, Williams, MT (2008). Effects of neonatal (+)-methamphetamine on path integration and spatial learning in rats: Effects of dose and rearing conditions. Int. J. Dev. Neurosci., 26: 599-610.
Herring, NR, Schaefer, TL, Tang, PH, Skelton, MR, Lucot, JP, Gudelsky, GA, Vorhees, CV, Williams, MT (2008). Comparison of time-dependent effects of (+)-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats. BMC Neurosci. 9: 49.
Skelton, MR, Williams, MT, Vorhees, CV (2008). Developmental effects of 3,4-methylenedioxymethamphetamine: A review. Behav. Pharmacol. 19: 91-111.
Schaefer, TL, Skelton, MR, Herring, NR, Gudelsky, GA, Vorhees, CV, Williams, MT (2008). Short- and long-term effects of multiple-day administration of (+)-methamphetamine or (±)-3,4-methylenedioxymethamphetamine on monoamine and corticosterone levels in the neonatal rats. J. Neurochem. 104: 1674-1685.
McAuliffe, JJ, Joseph, B, Hughes, E, Miles, L, Vorhees, CV (2008). Metallothionein I,II deficient mice do not exhibit significantly worse long-term behavioral outcomes following neonatal hypoxia-ischemia: MT I,II deficient mice have inherent behavioral impairments. Brain Res., 1190: 175-185.
Pan, D, Sciascia, A, II, Vorhees, CV, Williams, MT (2008). Progression of behavioral deficits during development in a murine model of Hurler syndrome. Brain Res., 1188: 241-253.
Grace, CE, Schaefer, TL, Herring, NR, Skelton, MR, McCrea, AE, Vorhees, CV, Williams, MT (2008). (+)-Methamphetamine increases corticosterone in plasma and BDNF in brain more than forced swim or isolation in neonatal rats. Synapse, 62: 110-121.
Lingrel, JB, Williams, MT, Vorhees, CV, Moseley, AE (2007). Na,K-ATPase and the role of the α isoforms. J. Bioenerg. Biomembr., 39: 385-389.
Vorhees, CV, Skelton, MR, Williams, MT (2007). Age-dependent effects of neonatal methamphetamine exposure on spatial learning. Behav. Pharmacol., 18: 549-562.
Skelton, MR, Williams, MT, Schaefer, TL, Vorhees, CV (2007). Neonatal methamphetamine increases brain-derived neurotrophic factor, but not nerve growth factor, during treatment and results in long-term spatial learning deficits. Psychoneuroendocrinology, 32: 734-745.
Siuciak, JA, McCarthy, SA, Chapin, DS, Reed, TM, Vorhees, CV, Repaske, DR (2007). Behavioral and neurochemical characterization of mice deficient in the phosphodiesterase 1B (PDE1B) enzyme. Neuropharmacology, 53: 113-124.
Vorhees, CV, Schaefer, TL, Williams, MT (2007). Developmental effects of 3,4-methylenedioxymethamphetamine on spatial versus path integration learning: Effects of dose distribution. Synapse, 61: 488-499.
McAuliffe, JJ, Joseph, B, Vorhees, CV (2007). Isoflurane delayed pre-conditioning reduces immediate mortality and improves striatal function in adult mice following neonatal hypoxia-ischemia. Anes. Analges., 104: 1066-1077.
Williams, MT, Herring, NR, Schaefer, TL, Skelton, MR, Campbell, NG, Lipton, JW, McCrea, AE, Vorhees, CV (2007). Alterations in body temperature, corticosterone, and behavior following the administration of 5-methoxy-diisopropyltryptamine (‘Foxy’) to adult rats: A new drug of abuse. Neuropsychopharmacology, 32: 1404-1420.
Moseley, AE, Williams, MT, Schaefer, TL, Bohanan, CS, Neumann, JC, Behbehani, MM, Vorhees, CV, Lingrel, JB (2007). Deficiency in Na,K-ATPase α isoform genes alters spatial learning, motor activity and anxiety in mice. J. Neurosci., 27: 616-626.

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.