Noboru Hiroi

Associate Professor
Molecular mechanisms of substance abuse and movement disorders.

 

Laboratory of Molecular Psychobiology

Our research focuses on the genetic mechanisms underlying pathological conditions of the central nervous system. Genetic variation contributes to many psychiatric conditions, including addiction and schizophrenia, but the precise genetic mechanisms of these disorders are still poorly understood. Our laboratory uses genetically engineered mouse models to ascertain the contribution of individual genes to specific psychiatric conditions. Our analysis integrates behavioral, anatomical and molecular approaches.
Ongoing projects investigate:

1) Transcriptional cascade of nicotine addiction.
2) Phosphorylation cascade of nicotine addiction.
3) Transcriptional cascade of cell death of dopaminergic neurons.
4) Monoamine oxidases and nicotine addiction.
5) Genetic basis of schizophrenia associated with velocardiofacial syndrome (VCFS).

 

Selected Publications

Zhu H, Lee M, Agatsuma S, Hiroi N. (2007) Pleiotropic impact of constitutive fosB inactivation on nicotine-induced behavioral alterations and stress-related traits in mice. Hum Mol Genet. 16(7):820-36.

Hiroi, N, Zhu H, Lee M, Funke B, Arai M, Itokawa M, Kucherlapati R, Morrow B, Sawamura T, Agatsuma S. (2005) A 200-kb region of human chromosome 22q11.2 confers antipsychotic-responsive behavioral abnormalities in mice. Proc Natl Acad Sci U S A. 102(52):19132-7.  

Zhu H, Lee M, Guan F, Agatsuma S, Scott D, Fabrizio K, Fienberg AA, Hiroi N. (2005) DARPP-32 phosphorylation opposes the behavioral effects of nicotine. Biol Psychiatry. 58(12):981-9.  

Hiroi N, Agatsuma S. (2005) Genetic susceptibility to substance dependence. Mol Psychiatry. 10(4):336-44. Feature Review.  

Lee M, Chen K, Shih JC, Hiroi N. (2004) MAO-B knockout mice exhibit deficient habituation of locomotor activity but normal nicotine intake. Genes Brain Behav. 3(4):216-27.  

Grande C, Zhu H, Martin AB, Lee M, Ortiz O, Hiroi N, Moratalla R. (2004) Chronic treatment with atypical neuroleptics induces striosomal FosB/DeltaFosB expression in rats. Biol Psychiatry. 55(5):457-63.  

Hiroi N, Fienberg AA, Haile CN, Alburges M, Hanson GR, Greengard P, Nestler EJ.(1999) Neuronal and behavioural abnormalities in striatal function in DARPP-32-mutant mice. Eur J Neurosci . 11(3):1114-8.  

Fienberg AA, Hiroi N, Mermelstein PG, Song W, Snyder GL, Nishi A, Cheramy A, O'Callaghan JP, Miller DB, Cole DG, Corbett R, Haile CN, Cooper DC, Onn SP, Grace AA, Ouimet CC, White FJ, Hyman SE, Surmeier DJ, Girault J, Nestler EJ, Greengard P. (1998) DARPP-32: regulator of the efficacy of dopaminergic neurotransmission. Science. 281(5378):838-42.

Rocha BA, Scearce-Levie K, Lucas JJ, Hiroi N, Castanon N, Crabbe JC, Nestler EJ, Hen R. (1998) Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor. Nature. 393(6681):175-8.  

Hiroi N, Brown JR, Haile CN, Ye H, Greenberg ME, Nestler EJ. (1997) FosB mutant mice: loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine's psychomotor and rewarding effects. Proc Natl Acad Sci U S A. 94(19):10397-402.  

Berhow MT, Hiroi N, Kobierski LA, Hyman SE, Nestler EJ. (1996) Influence of cocaine on the JAK-STAT pathway in the mesolimbic dopamine system . J Neurosci. 16(24):8019-26.  

Hiroi N, Graybiel AM. (1996) Atypical and typical neuroleptic treatments induce distinct programs of transcription factor expression in the striatum. J Comp Neurol. 374(1):70-83.  

Berhow MT , Hiroi N, Nestler EJ. (1996) Regulation of ERK (extracellular signal regulated kinase), part of the neurotrophin signal transduction cascade, in the rat mesolimbic dopamine system by chronic exposure to morphine or cocaine. J Neurosci. 16(15):4707-15.  

Xu M, Moratalla R, Gold LH, Hiroi N, Koob GF, Graybiel AM, Tonegawa S. (1994) Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses. Cell. 79(4):729-42.