Neocortical Gene Expression Associated with Behavioral Sensitization to Psychostimulants

  • Yasushi Kajii
  • Takanori Hashimoto
  • Asami Umino
  • Toru Nishikawa
Part of the Advances in Behavioral Biology book series (ABBI, volume 53)


Experience with amphetamine-like psychostimulants, such as amphetamine, methamphetamine (MAP) or cocaine, results in enhanced neuronal and behavioral responses to subsequent drug exposure. This behavioral sensitization, which is believed to be a part of the mechanisms sustaining drug addiction and drug-induced psychosis in human beings1, is a long-lasting adaptation to drugs of abuse based on persistent cellular and neurochemical changes in some specific brain circuits including the ventral tegmental area (VTA), nucleus accumbens (NAc) and cerebral cortex2. This type of brain plasticity seems to require the gene expression that drives the cascade leading to the establishment and maintenance of the sensitized behavioral responsiveness to stimulants or stress because the application of protein synthesis inhibitors blocks the induction of the sensitization3. Therefore, identification of the stimulant-responsive gene expression that is specifically observed under sensitization-inducing conditions affords helpful clues to understanding the molecular and neuronal mechanism of this unique behavioral plasticity.


Ventral Tegmental Area Behavioral Sensitization Mesocortical Dopamine Stimulant Sensitization Sensitization Regimen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    M. Sato, A lasting vulnerability to psychosis in patients with previous methamphetamine psychosis, Ann N Y Acad Sci 654, 160–170 (1992).PubMedCrossRefGoogle Scholar
  2. 2.
    L. J. M. J. Vanderscuren and P. W. Kalivas, Alternations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization; a critical review of preclinical studies. Psychopharmacology 151, 99–120 (2000).CrossRefGoogle Scholar
  3. 3.
    R. Karler, K. T. Finnegan, and L. D. Calder, Blockade of behavioral sensitization to cocaine and amphetamine by inhibitors of protein synthesis, Brain Res. 603, 19–24 (1993).PubMedCrossRefGoogle Scholar
  4. 4.
    T. M. Tzschentke, Pharmacology and behavioral pharmacology of the mesocortical dopamine system, Prog. Neurobiol. 63,: 241–320 (2001).PubMedCrossRefGoogle Scholar
  5. 5.
    S. R. Sesack and V. M. Pickel, Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area, J. Comp. Neurol. 320, 145–160 (1992).PubMedCrossRefGoogle Scholar
  6. 6.
    E. J. Nestler, Molecular basis of long-term plasticity underlying addiction, Nat. Rev. Neurosci. 2, 119–128 (2001).PubMedCrossRefGoogle Scholar
  7. 7.
    T. Hashimoto, Y. Kajii, and T. Nishikawa, Psychotomimetics-induction of tissue plasminogen activator mRNA in corticostriatal neurons in rat brain, Eur. J. Neurosci. 10, 3387–3399 (1998).PubMedCrossRefGoogle Scholar
  8. 8.
    Z. Qian, M. E. Gilbert, M. A. Colicos, E. R. Kandel, and D. Kuhl, Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation, Nature 361, 453–457 (1993).PubMedCrossRefGoogle Scholar
  9. 9.
    Y.-Y. Huang, M. E. Bach, H.-P. Lipp et al, Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways, Proc. Natl. Acad. Sci. USA 93, 8699–9704 (1996).PubMedCrossRefGoogle Scholar
  10. 10.
    R. Madani, S. Hulo, N. Toni et al, Enhanced hippocampal long-term potentiation and learning by increased neuronal expression of tissue-type plasminogen activator in transgenic mice, EMBO J. 18, 3007–3012 (1999).PubMedCrossRefGoogle Scholar
  11. 11.
    T. E. Robinson and B. Kolb, Alternations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine, Eur. J. Neurosci. 11, 1598–1604 (1999).PubMedCrossRefGoogle Scholar
  12. 12.
    R. E. Harlan and M. M. Garcia, Drugs of abuse and immediate-early genes in the forebrain. Mol. Neurobiol. 16, 221–267 (1998).PubMedCrossRefGoogle Scholar
  13. 13.
    E. J. Curran, H. Akil, and S. J. Watson, Psychomotor stimulant- and opiate-induced c-fos mRNA expression patterns in the rat forebrain: comparisons between acute drug treatment and a drug challenge in sensitized animals, Neurochem. Res. 21, 1425–1435 (1996).PubMedCrossRefGoogle Scholar
  14. 14.
    T. Nishikawa, A. Umino, A. Kashiwa, A. Ooshima, N. Nomura, and K. Takahashi, Stimulant-induced behavioral sensitization and cerebral neurotransmission, in: Neurotransmitters in neuronal plasticity and psychiatric disorders, edited by M. Tom (Excerpta Medica, Tokyo, 1993), pp53–62.Google Scholar
  15. 15.
    Y. Fujiwara, M. Kazahaya, M. Nakashima, and S. Ootsuki, Behavioral sensitization to methamphetamine in the rat: an ontogenic study, Psychopharmacology 91, 316–319, 1987.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Yasushi Kajii
    • 1
  • Takanori Hashimoto
    • 1
  • Asami Umino
    • 1
  • Toru Nishikawa
    • 1
    • 2
  1. 1.Department of Mental Disorder Research, National Institute of NeuroscienceNational Center of Neurology and PsychiatryKodaira, TokyoJapan
  2. 2.Section of Psychiatry and Behavioral ScienceTokyo Medical and Dental University Graduate SchoolBunkyo-ku, TokyoJapan

Personalised recommendations