Skip to main content

Advertisement

SpringerLink
Log in

Stimulant-induced psychosis and schizophrenia: The role of sensitization

  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Three different conditions, psychostimulant-induced behavioral sensitization in rodents, psychostimulantinduced psychoses in human, and chronic schizophrenia show similar longitudinal alternations, progressively enhanced susceptibility to abnormal behaviors, psychotic state, and relapse. Sensitization phenomena to the drugs or endogenous dopamine should be involved in the mechanisms underlying the development of such susceptibility. Recently, an enhanced dopamine release in vivo by amphetamine administration in the striatum has been shown in schizophrenics, which is a replication of that previously proven in the behavioral sensitization in rats. Accordingly, common molecular mechanisms of sensitization phenomena must develop in these three conditions, and are overviewed in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Akiyama K, Kanzaki A, Tsuchida K, et al.: Methamphetamineinduced behavioral sensitization and its implications for relapse of schizophrenia. Schizophr Res 1994, 12:251–257.

    Article  PubMed  CAS  Google Scholar 

  2. Robinson TE, Becker JB: Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res Rev 1986, 11:157–198.

    Article  CAS  Google Scholar 

  3. Laruelle M: The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. Brain Res Brain Res Rev 2000, 31:371–384. An important article.

    Article  PubMed  CAS  Google Scholar 

  4. Paulson PE, Camp DM, Robinson TE: Time course of transient behavioral depression and persistent behavioral sensitization in relation to regional brain monoamine concentrations during amphetamine withdrawal in rats. Psychopharmacology 1991, 103:480–492.

    Article  PubMed  CAS  Google Scholar 

  5. Hooks MS, Jones DN, Holtzman SG, et al.: Individual differences in behavior following amphetamine, GBR-12909, or apomorphine but not SKF-38393 or quinpirole. Psychopharmacology 1994, 116:217–225.

    Article  PubMed  CAS  Google Scholar 

  6. Alexander RC, Wright R, Freed W: Quantitative trait loci contributing to phencyclidine-induced and amphetamineinduced locomotor behavior in inbred mice. Neuropsychopharmacology 1996, 15:484–490.

    Article  PubMed  CAS  Google Scholar 

  7. Cunningham ST, Finn M, Kelley AE: Sensitization of the locomotor response to psychostimulants after repeated opiate exposure: role of the nucleus accumbens. Neuropsychopharmacology 1997, 16:147–155.

    Article  PubMed  CAS  Google Scholar 

  8. Lamarque S, Taghzouti K, Simon H: Chronic treatment with Delta(9)-tetrahydrocannabinol enhances the locomotor response to amphetamine and heroin. Implications for vulnerability to drug addiction. Neuropharmacology 2001, 41:118–129.

    Article  PubMed  CAS  Google Scholar 

  9. Horger BA, Giles MK, Schenk S: Preexposure to amphetamine and nicotine predisposes rats to self-administer a low dose of cocaine. Psychopharmacology 1992, 107:271–276.

    Article  PubMed  CAS  Google Scholar 

  10. Antelman SM, Eichler AJ, Black CA, et al.: Interchangeability of stress and amphetamine in sensitization. Science 1980, 207:329–331.

    Article  PubMed  CAS  Google Scholar 

  11. Shaham Y, Erb S, Stewart J: Stress-induced relapse to heroin and cocaine seeking in rats: a review. Brain Res Brain Res Rev 2000, 33:13–33.

    Article  PubMed  CAS  Google Scholar 

  12. Sato M, Chen CC, Akiyama K, et al.: Acute exacerbation of paranoid psychotic state after long-term abstinence in patients with previous methamphetamine psychosis. Biol Psychiatry 1983, 18:429–440.

    PubMed  CAS  Google Scholar 

  13. Tatetsu S: Methamphetamine psychosis. Folia Pstchiatr Neurol Jpn Suppl 1963, 7:377–380.

    Google Scholar 

  14. Satel SL, Edell WS: Cocaine-induced paranoia and psychosis proneness. Am J Psychiatry 1991, 148:1708–1711.

    PubMed  CAS  Google Scholar 

  15. Ohmori T, Ito K, Abekawa T, et al.: Psychotic relapse and maintenance therapy in paranoid schizophrenia: a 15 year follow up. Eur Arch Psychiatry Clin Neurosci 1999, 249:73–78. A good review.

    Article  PubMed  CAS  Google Scholar 

  16. Lieberman JA, Kane JM, Alvir J: Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology 1987, 91:415–433.

    Article  PubMed  CAS  Google Scholar 

  17. Lieberman JA, Kane JM, Sarantakos S, et al.: Prediction of relapse in schizophrenia. Arch Gen Psychiatry 1987, 44:597–603.

    PubMed  CAS  Google Scholar 

  18. Kazahaya Y, Akimoto K, Otsuki S: Subchronic methamphetamine treatment enhances methamphetamine- or cocaineinduced dopamine efflux in vivo. Biol Psychiatry 1989, 25:903–912.

    Article  PubMed  CAS  Google Scholar 

  19. Akimoto K, Hamamura T, Otsuki S: Subchronic cocaine treatment enhances cocaine-induced dopamine efflux, studied by in vivo intracerebral dialysis. Brain Res 1989, 490:339–344.

    Article  PubMed  CAS  Google Scholar 

  20. Akimoto K, Hamamura T, Kazahaya Y, et al.: Enhanced extracellular dopamine level may be the fundamental neuropharmacological basis of cross-behavioral sensitization between methamphetamine and cocaine: an in vivo dialysis study in freely moving rats. Brain Res 1990, 507:344–346.

    Article  PubMed  CAS  Google Scholar 

  21. Robinson TE, Jurson PA, Bennett JA, et al.: Persistent sensitization of dopamine neurotransmission in ventral striatum (nucleus accumbens) produced by prior experience with (+)-amphetamine: a microdialysis study in freely moving rats. Brain Res 1988, 462:211–222.

    Article  PubMed  CAS  Google Scholar 

  22. Hamamura T, Akiyama K, Akimoto K, et al.: Co-administration of either a selective D1 or D2 dopamine antagonist with methamphetamine prevents methamphetamine-induced behavioral sensitization and neurochemical change, studied by in vivo intracerebral dialysis. Brain Res 1991, 546:40–46.

    Article  PubMed  CAS  Google Scholar 

  23. Ujike H, Onoue T, Akiyama K, et al.: Effects of selective D-1 and D-2 dopamine antagonists on development of methamphetamine-induced behavioral sensitization. Psychopharmacology 1989, 98:89–92.

    Article  PubMed  CAS  Google Scholar 

  24. Karler R, Calder LD, Chaudhry IA, et al.: Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801. Life Sci 1989, 45:599–606.

    Article  PubMed  CAS  Google Scholar 

  25. Wolf ME, White FJ, Hu XT: MK-801 prevents alterations in the mesoaccumbens dopamine system associated with behavioral sensitization to amphetamine. J Neurosci 1994, 14:1735–1745.

    PubMed  CAS  Google Scholar 

  26. Laruelle M, Abi-Dargham A, van Dyck CH, et al.: Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci U S A 1996, 93:9235–9240.

    Article  PubMed  CAS  Google Scholar 

  27. Breier A, Su TP, Saunders R, et al.: Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci U S A 1997, 94:2569–2574.

    Article  PubMed  CAS  Google Scholar 

  28. Terwilliger RZ, Beitner JD, Sevarino KA, et al.: A general role for adaptations in G-proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function. Brain Res 1991, 548:100–110.

    Article  PubMed  CAS  Google Scholar 

  29. Nestler EJ, Aghajanian GK: Molecular and cellular basis of addiction. Science 1997, 278:58–63.

    Article  PubMed  CAS  Google Scholar 

  30. Greengard P, Allen PB, Nairn AC: Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron 1999, 23:435–447.

    Article  PubMed  CAS  Google Scholar 

  31. Cunningham ST, Kelley AE: Hyperactivity and sensitization to psychostimulants following cholera toxin infusion into the nucleus accumbens. J Neurosci 1993, 13:2342–2350.

    PubMed  CAS  Google Scholar 

  32. Miserendino MJ, Nestler EJ, Behavioral sensitization to cocaine: modulation by the cyclic AMP system in the nucleus accumbens. Brain Res 1995, 674:299–306.

    Article  PubMed  CAS  Google Scholar 

  33. Steketee JD: Intra-A10 injection of H7 blocks the development of sensitization to cocaine. Neuroreport 1994, 6:69–72.

    Article  PubMed  CAS  Google Scholar 

  34. Tolliver BK, Ho LB, Reid MS, et al.: Evidence for involvement of ventral tegmental area cyclic AMP systems in behavioral sensitization to psychostimulants. J Pharmacol Exp Ther 1996, 278:411–420.

    PubMed  CAS  Google Scholar 

  35. Brandon EP, Logue SF, Adams MR, et al.: Defective motor behavior and neural gene expression in RIIbeta-protein kinase A mutant mice. J Neurosci 1998, 18:3639–3649.

    PubMed  CAS  Google Scholar 

  36. Xue CJ, Ng JP, Li Y, et al.: Acute and repeated systemic amphetamine administration: effects on extracellular glutamate, aspartate, and serine levels in rat ventral tegmental area and nucleus accumbens. J Neurochem 1996, 67:352–363.

    Article  PubMed  CAS  Google Scholar 

  37. Licata SC, Freeman AY, Pierce-Bancroft AF, et al.: Repeated stimulation of L-type calcium channels in the rat ventral tegmental area mimics the initiation of behavioral sensitization to cocaine. Psychopharmacology 2000, 152:110–118.

    Article  PubMed  CAS  Google Scholar 

  38. Karler R, Turkanis SA, Partlow LM, et al.: Calcium channel blockers and behavioral sensitization. Life Sci 1991, 49:165–170.

    Article  PubMed  CAS  Google Scholar 

  39. Itzhak Y: Modulation of cocaine- and methamphetamineinduced behavioral sensitization by inhibition of brain nitric oxide synthase. J Pharmacol Exp Ther 1997, 282:521–527.

    PubMed  CAS  Google Scholar 

  40. Itzhak Y, Ali SF, Martin JL, et al.: Resistance of neuronal nitric oxide synthase-deficient mice to cocaine-induced locomotor sensitization. Psychopharmacology 1998, 140:378–386.

    Article  PubMed  CAS  Google Scholar 

  41. Pierce RC, Bell K, Duffy P, et al.: Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization. J Neurosci 1996, 16:1550–1560.

    PubMed  CAS  Google Scholar 

  42. Horger BA, Iyasere CA, Berhow MT, et al.: Enhancement of locomotor activity and conditioned reward to cocaine by brainderived neurotrophic factor. J Neurosci 1999, 19:4110–4122.

    PubMed  CAS  Google Scholar 

  43. Pierce RC, Pierce-Bancroft AF, Prasad BM: Neurotrophin-3 contributes to the initiation of behavioral sensitization to cocaine by activating the Ras/Mitogen-activated protein kinase signal transduction cascade. J Neurosci 1999, 19:8685–8695.

    PubMed  CAS  Google Scholar 

  44. Berhow MT, Hiroi N, Nestler EJ: 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 1996, 16:4707–4715.

    PubMed  CAS  Google Scholar 

  45. Wang XB, Funada M, Imai Y, et al.: rGbeta1: a psychostimulant-regulated gene essential for establishing cocaine sensitization. J Neurosci 1997, 17:5993–6000.

    PubMed  CAS  Google Scholar 

  46. Takaki M, Ujike H, Kodama M, et al.: Two kinds of mitogen-activated protein kinase phosphatases, MKP-1 and MKP-3, are differently activated by acute and chronic methamphetamine treatment in the rat brain. J Neurochem 2001, 79:679–688. A good article.

    Article  PubMed  CAS  Google Scholar 

  47. Ujike H, Takaki M, Kuroda S: Neural plasticity-related genes and the behavioral sensitization phenomenon. Psychiatry Clin Neurosci 2002, In press.

  48. Carlezon WA, Jr., Thome J, Olson VG, et al.: Regulation of cocaine reward by CREB. Science 1998, 282:2272–2275. An important review.

    Article  PubMed  CAS  Google Scholar 

  49. Walters CL, Blendy JA: Different requirements for cAMP response element binding protein in positive and negative reinforcing properties of drugs of abuse. J Neurosci 2001, 21:9438–9444.

    PubMed  CAS  Google Scholar 

  50. Hope BT, Nye HE, Kelz MB, et al.: Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments. Neuron 1994, 13:1235–1244.

    Article  PubMed  CAS  Google Scholar 

  51. Chen J, Kelz MB, Hope BT, et al.: Chronic Fos-related antigens: stable variants of deltaFosB induced in brain by chronic treatments. J Neurosci 1997, 17:4933–4941.

    PubMed  CAS  Google Scholar 

  52. Bibb JA, Chen J, Taylor JR, et al.: Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 2001, 410:376–380. A good article.

    Article  PubMed  CAS  Google Scholar 

  53. Hiroi N, Fienberg AA, Haile CN, et al.: Neuronal and behavioral abnormalities in striatal function in DARPP-32-mutant mice. Eur J Neurosci 1999, 11:1114–1118.

    Article  PubMed  CAS  Google Scholar 

  54. Kelz MB, Chen J, Carlezon WJ, et al.: Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine. Nature 1999, 401:272–276. A good article.

    Article  PubMed  CAS  Google Scholar 

  55. Hiroi N, Brown JR, Haile CN, et al.: 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 1997, 94:10397–10402.

    Article  PubMed  CAS  Google Scholar 

  56. Karler R, Finnegan KT, Calder LD: Blockade of behavioral sensitization to cocaine and amphetamine by inhibitors of protein synthesis. Brain Res 1993, 603:19–24.

    Article  PubMed  CAS  Google Scholar 

  57. Shimosato K, Saito T: Suppressive effect of cycloheximide on behavioral sensitization to methamphetamine in mice. Eur J Pharmacol 1993, 234:67–75.

    Article  PubMed  CAS  Google Scholar 

  58. Fujiwara Y, Kazahaya Y, Nakashima M, et al.: Behavioral sensitization to methamphetamine in the rat: an ontogenic study. Psychopharmacology 1987, 91:316–319.

    Article  PubMed  CAS  Google Scholar 

  59. Ujike H, Tsuchida K, Akiyama K, et al.: Ontogeny of behavioral sensitization to cocaine. Pharmacol Biochem Behav 1995, 50:613–617.

    Article  PubMed  CAS  Google Scholar 

  60. Robinson TE, Kolb B: Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine. J Neurosci 1997, 17:8491–8497. A good review.

    PubMed  CAS  Google Scholar 

  61. Robinson TE, Kolb B: Alterations 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 1999, 11:1598–1604.

    Article  PubMed  CAS  Google Scholar 

  62. Takaki M, Ujike H, Kodama M, et al.: Increased expression of synaptophysin and staathmin mRNAs after methamphetamine administration in rat brain. Neuroreport 2001, 12:1055–1060.

    Article  PubMed  CAS  Google Scholar 

  63. Denovan-Wright EM, Newton RA, Armstrong JN, et al.: Acute administration of cocaine, but not amphetamine, increases the level of synaptotagmin IV mRNA in the dorsal striatum of rat. Mol Brain Res 1998, 55:350–354.

    Article  PubMed  CAS  Google Scholar 

  64. Iwata S, Hewlett GH, Ferrell ST, et al.: Increased in vivo phosphorylation state of neuromodulin and synapsin I in striatum from rats treated with repeated amphetamine. J Pharmacol Exp Ther 1996, 278:1428–1434.

    PubMed  CAS  Google Scholar 

  65. Kodama M, Akiyama K, Ujike H, et al.: A robust increase in expression of arc gene, an effector immediate early gene, in the rat brain after acute and chronic methamphetamine administration. Brain Res 1998, 796:273–283.

    Article  PubMed  CAS  Google Scholar 

  66. Ujike H, Takaki M, Kodama M, et al.: Gene expression related to synaptogenesis, neuritogenesis, and MAP kinase in behavioral sensitization to psychostimulants. Ann N Y Acad Sci 2002, In press. A good review.

Download references

Author information

Authors and Affiliations

  1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan

    Hiroshi Ujike MD, PhD

Authors
  1. Hiroshi Ujike MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ujike, H. Stimulant-induced psychosis and schizophrenia: The role of sensitization. Curr Psychiatry Rep 4, 177–184 (2002). https://doi.org/10.1007/s11920-002-0024-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11920-002-0024-7

Keywords

Search

Navigation