Dr. Geyer’s research group focuses on developing parallel behavioral paradigms in animals and humans for use in psychiatric drug discovery. The group currently includes five faculty members, Drs. Susan Powell, Victoria Risbrough, Xianjin Zhou, Jared Young, and Adam Halberstadt. Our combined laboratories use behavioral measures and psychopharmacological manipulations in rodents and humans to examine the roles of neurotransmitters in behavior, to develop animal models of human drug effects, and to explore information-processing deficits in psychiatric disorders. We use startle measures of habituation, prepulse inhibition, anxiety potentiation, and fear extinction that are deficient in psychiatric disorders and can be mimicked in rodents by pharmacological, developmental, and genetic manipulations. Under Dr. Risbrough’s leadership, the group is using a battery of startle tests in a prospective longitudinal Marine Resilience Study, paralleled by neurobiological studies of CRF systems in rodents. Dr. Geyer has developed a Behavioral Pattern Monitor for use in rats, mice, and humans. These systems provide cross-species translational and multivariate assessments of spatio-temporal patterns of exploratory behavior and are being used in comparisons of schizophrenia and bipolar mania in relationship to corresponding animal models. We have explored the effects of classical hallucinogens, dopaminergic psychostimulants, and both direct and indirect serotonin agonists to elucidate their respective mechanisms of action and to reveal the involvement of specific monoamine systems and receptors in behavioral responses to environmental stimuli and in processes such as arousal, habituation, and sensorimotor gating. Animal models of interest in the laboratory include pharmacological manipulations, a variety of developmental perturbations, and genetic models involving strain comparisons, knockouts, and humanized mutant mice, most of which are related to psychotic and/or stress-related disorders. A current focus of the laboratory is the development of murine tests of specific cognitive domains relevant to the MATRICS and CNTRICS efforts to treat cognitive deficits in schizophrenia.
Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: A decade in review. Psychopharmacol 156:117-154
Geyer MA, McIlwain KL, Paylor R (2002) Mouse genetic models for prepulse inhibition: An early review. Molecular Psychiatry 7:1039-1053
Doherty JM, Masten VL, Powell SB, Ralph RJ, Low MJ, Geyer MA. (2008) Contributions of dopamine D1, D2, and D3 receptor subtypes to the disruptive effects of cocaine on prepulse inhibition in mice. Neuropsychopharmacology, 33:2648-2656.
Geyer MA and Vollenweider FX (2008) Serotonin research: Contributions to understanding psychoses. Trends in Pharmacological Sciences, 29:445-453.
Geyer MA. (2008) Developing translational animal models for symptoms of schizophrenia or bipolar mania. Neurotoxicity Research, 14:71-78.
Young JW, Powell S, Risbrough VB, Marston HM, Geyer MA (2009) Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacology and Therapeutics. 122:150–202.
Risbrough VB, Geyer MA, Hauger RL, Coste S, Stenzel-Poore M, Wurst W, Holsboer F. (2009) CRF1 and CRF2 receptors required for potentiated startle to contextual but not discrete cues. Neuropsychopharmacology, 34:1494-503.
Powell SB, Zhou X, Geyer MA (2009) Prepulse inhibition and genetic mouse models of schizophrenia. Behavioural Brain Research, 204:282-94.
Perry W, Minassian A, Paulus MP, Young JW, Kincaid M, Ferguson E, Henry BL, Zhuang X, Masten VL, Sharp RF, Geyer MA. (2009) A reverse-translational study of dysfunctional exploration in psychiatric disorders: From Mice to Men. Archives of General Psychiatry, 66:1072-1080.
Zhou X, Nie Z, Roberts A, Zhang D, Sebat J, Malhotra D, Kelsoe JR, Geyer MA (2010) Reduced NMDAR1 expression in the Sp4 hypomorphic mouse may contribute to endophenotypes of human psychiatric disorders. Human Molecular Genetics, 19:3797-3805.
Geyer MA. (2010) New opportunities in the treatment of cognitive impairments associated with schizophrenia. Current Directions in Psychological Sciences, 19:264-269.
Young JW, Powell SB, Geyer MA. (2011) Mouse pharmacological models of cognitive disruption relevant to schizophrenia. Neuropharmacology, 62(3):1381-1390.