Neurology

Research Grants and Contracts

Investigator, Active

• Effects of lead, manganese and stress during development (NIH/NIEHS, 1 R01 ES015689-01 $1,250,000 direct costs over 5 years, 40% effort; 9-2006 – 6-30-2011).
• An Emotional Behavior Study in Sprague-Dawley CD/IGS Rats Given LY110140 Daily by Gavage from Postnatal Day (PND) 33 to 62. (Project Director. C.V. Vorhees, PI, M.T. Williams, Eli Lilly, 30% effort, 1/1/2007- 12/31/2007, $292,871 direct costs)
• Pending:
  None

Investigator, Pending

• The effects of 5-methoxy-diisopropyltryptamine 'Foxy'. (NIH/NIDA, 1 R21 DA019495-01).

Co-Investigator, Active

• Developmental Effects of Methamphetamine-like Stimulants. (PI: C.V. Vorhees, NIH/NIDA, 2 R01 DA06733-10, 10% effort, 4/1/2005-3/31/2010)
• Effects of neonatal MDMA on brain and behavior. (PI: C.V. Vorhees, NIH/NIDA, R01 DA021394, 20% effort 4/1/2006-3/31/2011).
• Training Grant in Teratology (PI: C.V. Vorhees, NIH/NIEHS, 2 T32 ES07051)
• Genetic Susceptibility to PCB-induced Developmental Neurotoxicity. (PI: C.V. Vorhees, Center for Environmental Genetics Pilot Project Grant, $25,000, 5/1/2007-4-30-2008)
• Genetic differences in PCB-induced behavior. (PI: D. W. Nebert, NIH/NIEHS, R21 ES015335, 10% effort, $438,193, 12/15/2007 – 11/30/2009).
• Pending:
  None

Co-Investigator, Inactive

• Developmental interactions of methamphetamine and stress. (NIH/NIDA, 1 K01 DA14269-05, $577,690, 2002-2007).
  ADHD phenotype network: Animal model to clinical trial. (PI: F. R. Sallee, NIH/NINDS, 1 R21 MH66212-01).
• Developmental Effects of Methylenedioxymethamphetamine. (PI: C.V. Vorhees, NIH/NIDA, 2 R01 DA 11902-03, 10% effort)
  

Publications, Most Recent

Skelton, M. R., Williams, M. T., McInturf, S.A., Rossi III, J., Aronow, B. J., Vorhees, C. V. (in preparation).  Neonatal exposure to ±3,4-methelynedioxymethamphetamine alters NMDA receptor subunit 1, nNOS and PSD95 expression and LTP in adult rats.

Herring, N. R., Gudelsky, G. A., Vorhees, C. V., Williams, M. T.  (submitted 5-28-2008).  Dissociation of dopaminergic neurotoxicity and path integration learning deficits from hyperthermia after (+)-methamphetamine treatment in adrenalectomized rats.

Vorhees, C. V., Schaefer, T. L., Skelton, M. R., Grace, C. E., Herring, N. R., Williams, M. T.  (accepted with minor revision).  ±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.  Developmental Neuroscience

Vorhees, C. V., Johnson, H. L., Burns, L. N., Williams, M. T.  (major revision, resubmitted 6-26-2008).  Effects of developmental quinpirole treatment on adult behavior. Neurotoxicology and Teratology

Loepke, A.W., Istaphanous, G.K., Miles, L., Hughes, E.A., McCann, J.C., Kurth, C.D., Williams, M.T., Vorhees, C.V., Danzer, S.C. (in press).  Effects of neonatal isoflurane anesthesia on neuronal structure and adult neurocognitive function in mice. Anesthesia & Analgesia

Skelton, M. R., Able, J. A., Grace, C. E., Herring, N.R., Schaefer, T. L., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (in press).  (±)-3,4-methylenedioxymethamphetamine treatment in adult rats impairs path integration learning: A comparison of single versus once per week treatment for five weeks.  Neuropharmacology

Sun, Y., Jia, L., Williams M. T., Zamzow, M., Ran, H., Quinn, B., Aronow, B.J., Vorhees, C. V., Witte, D. P., Grabowski, G. A. (in press).  Gene expression profiling and neurobehavioral assessments in prosaposin deficient mice: Molecular alterations precede neuronal deficits. BMC Neuroscience

Herring, N.R., Schaefer, T. L., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (in press).  Effect of (+)-methamphetamine on path integration learning, novel object recognition, and neurotoxicity in rats. Psychopharmacology

Vorhees, C. V., Herring, N.R., Schaefer, T. L., Grace, C. E., Skelton, M. R., Johnson, H. L., Williams, M. T. (2008).  Effects of (+)-methamphetamine on path integration and spatial learning in rats: Effects of dose and rearing conditions. International Journal of Developmental Neuroscience 26(6):599-610.

Sun, Y., Witte, D.P., Ran, H., Zamzow, M., Barnes, S., Cheng, H., Han, X., Williams, M.T., Skelton, M.R., Vorhees, C.V., Grabowski, G.A. (2008).  Neurological deficits and glycosphingolipid accumulation in Saposin B deficient mice.  Human Molecular Genetics 17:2345-2356.

Herring, N.R., Schaefer, T.L., Tang, P.H., Skelton, M.R., Lucot, J.P., Gudelsky, G.A., Vorhees, C.V., Williams, M.T. (2008).  Comparison of time-dependent effects of (+)-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats. BMC Neuroscience 9:49.

Skelton, M. R., Williams, M. T., Vorhees, C. V. (2008).  Developmental effects of 3,4-methylenedioxymethamphetamine: A review.  Behavioural Pharmacology 19(2):91-111.

Schaefer, T. L., Skelton, M. R., Herring, N.R., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (2008).  Short- and long-term effects of (+)-methamphetamine and (±)-3,4-methylenedioxymethamphetamine on monoamine and corticosterone levels in the neonatal rat following multiple days of treatment. Journal of Neurochemistry 104:1674-1685.

Pan, D., Sciascia, A., Vorhees, C. V., Williams, M. T. (2008).  Progression of multiple behavioral deficits during development in a murine model of Hurler Syndrome: Age of onset during development.  Brain Research, 1188:241-253.

Grace, C. E., Schaefer, T. L., Herring, N.R., Skelton, M. R., McCrea, A. E., Vorhees, C. V., Williams, M. T. (2008).  (+)-Methamphetamine increases corticosterone in plasma and BDNF in brain more than forced swim or isolation in neonatal rats. Synapse, 62(2):110-121.

Lingrel, J. B., Williams, M. T., Vorhees, C. V., Moseley A. E. (2007).  Na,K-ATPase and the role of α isoforms. J Bioenergetics and Biomembranes 39(5-6):385-9. (Review)

Vorhees, C. V., Skelton, M. R., Williams, M. T. (2007).  Age-dependent effects of neonatal methamphetamine exposure on spatial learning.  Behavioural Pharmacology, 18(5-6):549-562.

Skelton, M. R., Williams, M. T., Schaefer, T. L., Vorhees, C. V. (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(6): 734-745.

Williams, M. T.*, Herring, N.R.*, Schaefer, T. L., Skelton, M. R., Campbell N. G., Lipton, J. W., McCrea, A. E., Vorhees, C. V. (2007).  Alterations in corticosterone and behavior following the administration of 5-methoxy-diisopropyltryptamine (‘Foxy’) to adult rats: A new drug of abuse.  *denotes equal authorship.  Neuropsychopharmacology 32: 1404-1420.

Vorhees, C. V., Schaefer, T. L., Williams, M. T. (2007).  Developmental exposure to 3,4-methylenedioxymethamphetamine results in differential long-term deficits in spatial vs. path integration learning as a function of dose distribution. Synapse 61(7): 488-499.

Moseley A. E.*, Williams, M. T.*, Schaefer, T. L., Bohanan, C. S., Behbehani, M. M., Vorhees, C. V., Lingrel, J. B. (2007).  Deficiency in Na,K-ATPase alpha isoform genes alters spatial learning, motor activity and anxiety in mice.  *denotes equal authorship.  Journal of Neuroscience 27(3):616-626.

Skelton, M. R., Williams, M. T., Vorhees, C. V. (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 189(3):307-318.

Thacker, S. K., Perna, M. K., Ward, J. J., Schaefer, T. L., Williams, M. T., Kostrzewa, R. M., Brown, R. W. (2006).  The effects of adulthood olanzapine treatment on cognitive performance and neurotrophic factor content in male and female rats neonatally treated with quinpirole.  European Journal of Neuroscience. 24:2075-2083.

Williams, M. T., Furay, A. F., Ehrman, L. A., Schaefer, T. L., Vorhees, C. V. (2006).  Ontogeny of the adrenal response to (+)-methamphetamine in neonatal rats: the effect of prior drug exposure.Stress 9(3): 153-163.

Vorhees, C. V., Williams, M. T. (2006).  Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nature Protocols, 1(2): 848-858.

Schaefer, T. L., Ehrman, L. A., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (2006).  A comparison of monoamine and corticosterone levels 24 hours following d-methamphetamine, ±3,4-methylenedioxymethamphetamine, cocaine, d-fenfluramine, or methylphenidate administration in the neonatal rat. Journal of Neurochemistry 98(5): 1369-1378.

Ehrman, L. A., Williams, M. T., Schaefer, T. L., Gudelsky, G. A., Reed, T. M., Fienberg, A. A., Greengard, P., Vorhees, C. V. (2006).  Phosphodiesterase 1B modulates the effects of methamphetamine on locomotor activity and spatial learning through a DARPP32-dependent pathway: evidence from PDE1B-DARPP32 double knockout mice. Genes, Brain, and Behavior, 5: 540-551.

Able, J. A., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (2006).  ±3, 4-Methylenedioxymethamphetamine in adult rats produces deficits in path integration and spatial reference memory. Biological Psychiatry, 59(12): 1219-1226.

Crawford, C. A., Williams, M. T., Kohutek, J. L., Choi, F. A., Yoshida, S. T., McDougall, S. A., Vorhees, C. V. (2006).  Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPγS binding in adult rats. Brain Research, 1077: 178-186.

Brown, R. W., Perna, M. K., Schaefer, T. L., Williams, M. T. (2006).  The effects of nicotine on D2-mediated behaviors and neurotrophins of rats neonatally treated with quinpirole.  Synapse 59(5): 253-259.

Becker, L. A., Kunkel, A. J., Brown, M. R., Ball, E. E., Williams, M. T. (2005).  Effects of dietary phytoestrogen exposure during perinatal period. Neurotoxicology and Teratology 27(6):825-834.

Brunskill, E. W., Erhman, L. A., Williams, M. T., Klanke, J., Hammer, D., Schaefer, T. L., Sah, R., Dorn, G. W., Potter, S. S., Vorhees, C. V. (2005).  Abnormal neurodevelopmental, behavioral, and neurotransmitter signaling in NPAS-3 deficient mice. European Journal of Neuroscience 22(6): 1265-1276.

Cohen, M. A., Skelton, M. R., Schaefer, T. L., Gudelsky, G. A., Vorhees, C. V., Williams, M. T.  (2005).  Learning and memory after neonatal exposure to 3,4-methylenedioxymethamphetamine (ecstasy) in rats: Interaction with exposure in adulthood.Synapse 57(3): 148-159.

Williams, M. T., Schaefer, T. L., Ehrman, L. A., Able, J. A., Gudelsky, G. A., Sah, R., Vorhees, C. V. (2005).  3,4-Methylenedioxymethamphetamine administration on postnatal day 11 in rat increases pituitary-adrenal output and reduces striatal and hippocampal serotonin without altering SERT activity.  Brain Research 1039(1/2):95-105.

Vorhees, C. V., Reed, T. M., Morford, L. L., Fukumura, M., Wood, S. L., Brown, C. A., Skelton, M. R., McCrea, A. E., Rock, S. L., and Williams, M. T. (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).  Neurotoxicology and Teratology 27(1): 117-134.

Kuan, C.-Y., Schloemer, A. J., Lu, A., Burns, K. A., Weng, W.-L., Williams, M. T., Strauss, K. I., Vorhees, C. V., Flavell, R. A., Davis, R. J., Sharp, F. R., Rakic, P. (2004).  Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying neurons in adult rodent brain. Journal of Neuroscience 24(47):10763-10772.

Skelton, M. R., Blankemeyer, T. L., Gudelsky, G. A., Brown-Strittholt, C. A., Vorhees, C. V., Williams, M. T. (2004).  Metyrapone attenuates the sequential learning deficits, but not monoamine depletions following d,l-fenfluramine administration to adult rats.Synapse 54(4): 214-222.

Williams, M. T., Brown, C. A., Skelton, M. R., Vinks, A. A., and Vorhees, C. V.  (2004). Absorption and clearance of ±3,4-methylenedioxymethamphetamine from the plasma of neonatal rats. Neurotoxicology and Teratology 26(6): 849-856.

Vorhees, C. V., Reed, T. M., Skelton, M. R., and Williams, M. T. (2004).  Exposure to 3,4-methylenedioxymethamphetamine (MDMA) on postnatal days 11-20 induces reference but not working memory deficits in the Morris water maze in rats: implications of prior learning. International Journal of Developmental Neuroscience. 22(5/6): 247-259.

Williams, M. T., Moran, M. S., & Vorhees , C. V. (2004).  Behavioral and growth effects induced by low dose methamphetamine administration during the neonatal period in rats. International Journal of Developmental Neuroscience. 22(5/6): 273-283.

Brown, R. W., Flanigan, T. J., Thompson, K. N., Thacker, S. K., Schaefer, T. L., Williams, M. T. (2004).  Neonatal quinpirole treatment impairs Morris water task performance in early postweanling rats: Relationship to increases in corticosterone and decreases in neurotrophic factors.  Biological Psychiatry 56(3):161-168.

Williams, M. T.*, Brown, R. W.*, Vorhees, C. V.  (2004).  Neonatal methamphetamine administration induces region-specific long-term neuronal morphological changes in the rat hippocampus, nucleus accumbens, and parietal cortex. European Journal of Neuroscience 19(12): 3165-3170.  *denotes equal authorship.

Brown, R. W., Thompson, K. D., Thompson, K. N., Ward, J. J., Thacker, S. K., Williams, M. T., and Kostrzewa, R. M. (2004).  Adulthood nicotine treatment alleviates behavioral impairments in rats neonatally treated with quinpirole: Possible roles of acetylcholine function and neurotrophic factor expression.European Journal of Neuroscience 19(6): 1634-1642.

Williams, M. T., Blankemeyer, T. L., Schaefer, T. L., Brown, C. A., Gudelsky, G. A., Vorhees, C. V. (2003).  Long-term effects of neonatal methamphetamine exposure in rats on spatial learning in the Barnes maze and on cliff avoidance, corticosterone release, and neurotoxicity in adulthood.  Dev Brain Res 147(1-2): 163-175.

Williams, M. T., Moran, M. S., & Vorhees , C. V. (2003) Refining the critical period for methamphetamine-induced spatial deficits in the Morris water maze. Psychopharmacology 168, 329-338.

Williams, M. T., Morford, L. L., Wood, S. L., Wallace, T. L., Fukumura, M., Broening, H. W., and Vorhees, C. V. (2003).  Developmental d-methamphetamine treatment selectively induces spatial navigation impairments in reference memory in the Morris water maze while sparing working memory.  Synapse 48, 138-148.

Crawford, C. A., Williams, M. T., Newman, E. R., McDougall S. A., & Vorhees, C. V. (2003) Methamphetamine exposure during the preweanling period causes prolonged changes in dorsal striatal protein kinase A activity, dopamine D2-like binding sites, and dopamine content. Synapse 48, 131-137.

Williams, M. T., Morford, L. L., Wood, S. L., Rock, S. L., McCrea, A. E., Fukumura, M., Wallace, T. L., Broening, H. W., Moran, M. S., & Vorhees, C. V. (2003).  Developmental 3,4-methylenedioxymethamphetamine (MDMA)-induced learning deficits are not related to undernutrition or litter effects: novel use of litter size to control for MDMA-induced growth decrements.  Brain Research 968 (1), 89-101.

Related Areas

This person works in these other areas at Cincinnati Children's Hospital Medical Center: