Skip to main content
SpringerLink
Log in

The amphetamine sensitization model of schizophrenia: relevance beyond psychotic symptoms?

  • Review
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

A sensitized dopamine system may be linked to the genesis of psychotic symptoms in schizophrenia. Following withdrawal from amphetamine exposures, psychotic-like traits have been robustly demonstrated, but the presence of cognitive/mnemonic deficits remains uncertain.

Methods

Adult male Lewis and Fischer rats, differing in cognitive performance, were exposed intermittently to escalating doses of amphetamine over 5 weeks. This was effective in producing behavioral sensitization to a subsequent amphetamine challenge. Following 27 days of drug withdrawal, the animals were assessed in Pavlovian conditioning, object recognition, and spatial working memory. In addition, prepulse inhibition (PPI), spontaneous motor activity, and anxiety-like behavior were measured.

Results

Amphetamine pretreatment induced behavioral sensitization in both rat strains similarly. Working memory was enhanced in Fischer but not Lewis rats following withdrawal. Spontaneous novel object preference was enhanced in sensitized Fischer rats, but was impaired in sensitized Lewis rats, thus effectively reversing the strain difference in non-sensitized controls. In contrast, Pavlovian fear conditioning remained unaffected and so were anxiety-like behavior, open field activity, and PPI.

Conclusion

The face validity of the amphetamine withdrawal model for cognitive deficits was limited to the object recognition memory impairment observed in sensitized Lewis rats. Yet, the possibility that enhancing dopaminergic neurotransmission may facilitate object recognition and spatial working memory performance was demonstrated in sensitized Fischer rats. Identification of the mechanisms underlying such strain-dependent effects would be instrumental in the further specifications of the construct validity, and therefore the limitations and potential of the amphetamine sensitization model of schizophrenia.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M (1998) Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 155:761–767

    PubMed  CAS  Google Scholar 

  • Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL, Gorman JM, Laruelle M (2000) Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci U S A 97:8104–8109

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Barch DM, Carter CS (2005) Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers. Schizophr Res 77:43–58

    Article  PubMed  Google Scholar 

  • Barker GR, Bird F, Alexander V, Warburton EC (2007) Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex. J Neurosci 27:2948–2957

    Article  PubMed  CAS  Google Scholar 

  • Beitner-Johnson D, Guitart X, Nestler EJ (1991) Dopaminergic brain reward regions of Lewis and Fischer rats display different levels of tyrosine hydroxylase and other morphine- and cocaine-regulated phosphoproteins. Brain Res 561:147–150

    Article  PubMed  CAS  Google Scholar 

  • Beitner-Johnson D, Guitart X, Nestler EJ (1992) Common intracellular actions of chronic morphine and cocaine in dopaminergic brain reward regions. Ann N Y Acad Sci 654:70–87

    Article  PubMed  CAS  Google Scholar 

  • Beitner-Johnson D, Guitart X, Nestler EJ (1993) Glial fibrillary acidic protein and the mesolimbic dopamine system: regulation by chronic morphine and Lewis–Fischer strain differences in the rat ventral tegmental area. J Neurochem 61:1766–1773

    Article  PubMed  CAS  Google Scholar 

  • Braff DL, Light GA (2004) Preattentional and attentional cognitive deficits as targets for treating schizophrenia. Psychopharmacology (Berl) 174:75–85

    Article  CAS  Google Scholar 

  • Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A, Weinberger DR, Weisenfeld N, Malhotra AK, Eckelman WC, Pickar D (1997) 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 94:2569–2574

    Article  PubMed  CAS  Google Scholar 

  • Brodkin ES, Carlezon WA Jr, Haile CN, Kosten TA, Heninger GR, Nestler EJ (1998) Genetic analysis of behavioral, neuroendocrine, and biochemical parameters in inbred rodents: initial studies in Lewis and Fischer 344 rats and in A/J and C57BL/6J mice. Brain Res 805:55–68

    Article  PubMed  CAS  Google Scholar 

  • Cador M, Dulluc J, Mormede P (1993) Modulation of the locomotor response to amphetamine by corticosterone. Neuroscience 56:981–988

    Article  PubMed  CAS  Google Scholar 

  • Camp DM, Browman KE, Robinson TE (1994) The effects of methamphetamine and cocaine on motor behavior and extracellular dopamine in the ventral striatum of Lewis versus Fischer 344 rats. Brain Res 668:180–193

    Article  PubMed  CAS  Google Scholar 

  • Castner SA, Vosler PS, Goldman-Rakic PS (2005) Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex. Biol Psychiatry 57:743–751

    Article  PubMed  CAS  Google Scholar 

  • Dalla C, Antoniou K, Kokras N, Drossopoulou G, Papathanasiou G, Bekris S, Daskas S, Papadopoulou-Daifoti Z (2008) Sex differences in the effects of two stress paradigms on dopaminergic neurotransmission. Physiol Behav 93:595–605

    Article  PubMed  CAS  Google Scholar 

  • Davis KL, Kahn RS, Ko G, Davidson M (1991) Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 148:1474–1486

    PubMed  CAS  Google Scholar 

  • Deacon TW, Eichenbaum H, Rosenberg P, Eckmann KW (1983) Afferent connections of the perirhinal cortex in the rat. J Comp Neurol 220:168–190

    Article  PubMed  CAS  Google Scholar 

  • Del Arco A, Mora F (2001) Dopamine release in the prefrontal cortex during stress is reduced by the local activation of glutamate receptors. Brain Res Bull 56:125–130

    Article  PubMed  Google Scholar 

  • Dhabhar FS, McEwen BS, Spencer RL (1993) Stress response, adrenal steroid receptor levels and corticosteroid-binding globulin levels—a comparison between Sprague–Dawley, Fischer 344 and Lewis rats. Brain Res 616:89–98

    Article  PubMed  CAS  Google Scholar 

  • Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A 85:5274–5278

    Article  PubMed  Google Scholar 

  • Elvevag B, Goldberg TE (2000) Cognitive impairment in schizophrenia is the core of the disorder. Crit Rev Neurobiol 14:1–21

    PubMed  CAS  Google Scholar 

  • Ersche KD, Clark L, London M, Robbins TW, Sahakian BJ (2006) Profile of executive and memory function associated with amphetamine and opiate dependence. Neuropsychopharmacology 31:1036–1047

    Article  PubMed  CAS  Google Scholar 

  • Featherstone RE, Rizos Z, Kapur S, Fletcher PJ (2008) A sensitizing regimen of amphetamine that disrupts attentional set-shifting does not disrupt working or long-term memory. Behav Brain Res 189:170–179

    Article  PubMed  CAS  Google Scholar 

  • Feldon J, Weiner I (1992) From an animal model of an attentional deficit towards new insights into the pathophysiology of schizophrenia. J Psychiatr Res 26:345–366

    Article  PubMed  CAS  Google Scholar 

  • Fletcher PJ, Tenn CC, Rizos Z, Lovic V, Kapur S (2005) Sensitization to amphetamine, but not PCP, impairs attentional set shifting: reversal by a D(1) receptor agonist injected into the medial prefrontal cortex. Psychopharmacology (Berl) 183:190–200

    Article  CAS  Google Scholar 

  • Fletcher PJ, Tenn CC, Sinyard J, Rizos Z, Kapur S (2007) A sensitizing regimen of amphetamine impairs visual attention in the 5-choice serial reaction time test: reversal by a D1 receptor agonist injected into the medial prefrontal cortex. Neuropsychopharmacology 32:1122–1132

    Article  PubMed  CAS  Google Scholar 

  • Flores G, Wood GK, Barbeau D, Quirion R, Srivastava LK (1998) Lewis and Fischer rats: a comparison of dopamine transporter and receptors levels. Brain Res 814:34–40

    Article  PubMed  CAS  Google Scholar 

  • George FR, Porrino LJ, Ritz MC, Goldberg SR (1991) Inbred rat strain comparisons indicate different sites of action for cocaine and amphetamine locomotor stimulant effects. Psychopharmacology (Berl) 104:457–462

    Article  CAS  Google Scholar 

  • Geyer MA (2006) The family of sensorimotor gating disorders: comorbidities or diagnostic overlaps? Neurotox Res 10:211–220

    Article  PubMed  CAS  Google Scholar 

  • 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. Psychopharmacology (Berl) 156:117–154

    Article  CAS  Google Scholar 

  • Gold JM, Carpenter C, Randolph C, Goldberg TE, Weinberger DR (1997) Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia. Arch Gen Psychiatry 54:159–165

    PubMed  CAS  Google Scholar 

  • Goldberg TE, Bigelow LB, Weinberger DR, Daniel DG, Kleinman JE (1991) Cognitive and behavioral effects of the coadministration of dextroamphetamine and haloperidol in schizophrenia. Am J Psychiatry 148:78–84

    PubMed  CAS  Google Scholar 

  • Goldberg TE, Patterson KJ, Taqqu Y, Wilder K (1998) Capacity limitations in short-term memory in schizophrenia: tests of competing hypotheses. Psychol Med 28:665–673

    Article  PubMed  CAS  Google Scholar 

  • Goldberg TE, Weinberger DR, Berman KF, Pliskin NH, Podd MH (1987) Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Arch Gen Psychiatry 44:1008–1014

    PubMed  CAS  Google Scholar 

  • Goldman-Rakic PS (1994) Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci 6:348–357

    PubMed  CAS  Google Scholar 

  • Gray JA, Feldon J, Rawlins JNP, Smith AD, Hemsley DR (1991) The neuropsychology of schizophrenia. Behav Brain Sci 14:1–84

    Google Scholar 

  • Green MF (2006) Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry 67:3–8 discussion 36–42

    Article  PubMed  Google Scholar 

  • Green MF, Nuechterlein KH (1999) Should schizophrenia be treated as a neurocognitive disorder? Schizophr Bull 25:309–319

    PubMed  CAS  Google Scholar 

  • Guitart X, Beitner-Johnson D, Marby DW, Kosten TA, Nestler EJ (1992) Fischer and Lewis rat strains differ in basal levels of neurofilament proteins and their regulation by chronic morphine in the mesolimbic dopamine system. Synapse 12:242–253

    Article  PubMed  CAS  Google Scholar 

  • Guitart X, Kogan JH, Berhow M, Terwilliger RZ, Aghajanian GK, Nestler EJ (1993) Lewis and Fischer rat strains display differences in biochemical, electrophysiological and behavioral parameters: studies in the nucleus accumbens and locus coeruleus of drug naive and morphine-treated animals. Brain Res 611:7–17

    Article  PubMed  CAS  Google Scholar 

  • Hannesson DK, Howland JG, Phillips AG (2004) Interaction between perirhinal and medial prefrontal cortex is required for temporal order but not recognition memory for objects in rats. J Neurosci 24:4596–4604

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, Sorg BA, Hooks MS (1993) The pharmacology and neural circuitry of sensitization to psychostimulants. Behav Pharmacol 4:315–334

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, Stewart J (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Brain Res Rev 16:223–244

    Article  PubMed  CAS  Google Scholar 

  • Katzev RD, Mills SK (1974) Strain differences in avoidance conditioning as a function of the classical CS–US contingency. J Comp Physiol Psychol 87:661–671

    Article  PubMed  CAS  Google Scholar 

  • Kirrane RM, Mitropoulou V, Nunn M, New AS, Harvey PD, Schopick F, Silverman J, Siever LJ (2000) Effects of amphetamine on visuospatial working memory performance in schizophrenia spectrum personality disorder. Neuropsychopharmacology 22:14–18

    Article  PubMed  CAS  Google Scholar 

  • Kolb B, Gorny G, Li Y, Samaha AN, Robinson TE (2003) Amphetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens. Proc Natl Acad Sci U S A 100:10523–10528

    Article  PubMed  CAS  Google Scholar 

  • Kosten TA, Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35–69

    Article  PubMed  CAS  Google Scholar 

  • Laruelle M (1998) Imaging dopamine transmission in schizophrenia. A review and meta-analysis. Q J Nucl Med 42:211–221

    PubMed  CAS  Google Scholar 

  • Laruelle M (2000) The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. Brain Res Brain Res Rev 31:371–384

    Article  PubMed  CAS  Google Scholar 

  • Lieberman JA, Sheitman BB, Kinon BJ (1997) Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity. Neuropsychopharmacology 17:205–229

    Article  PubMed  CAS  Google Scholar 

  • Lindley SE, Bengoechea TG, Wong DL, Schatzberg AF (1999) Strain differences in mesotelencephalic dopaminergic neuronal regulation between Fischer 344 and Lewis rats. Brain Res 832:152–158

    Article  PubMed  CAS  Google Scholar 

  • Lisman JE, Grace AA (2005) The hippocampal-VTA loop: controlling the entry of information into long-term memory. Neuron 46:703–713

    Article  PubMed  CAS  Google Scholar 

  • McCann DJ (2008) Potential of buprenorphine/naltrexone in treating polydrug addiction and co-occurring psychiatric disorders. Clin Pharmacol Ther 83:627–630

    Article  PubMed  CAS  Google Scholar 

  • McIntyre DC, Kelly ME, Staines WA (1996) Efferent projections of the anterior perirhinal cortex in the rat. J Comp Neurol 369:302–318

    Article  PubMed  CAS  Google Scholar 

  • McNab F, Varrone A, Farde L, Jucaite A, Bystritsky P, Forssberg H, Klingberg T (2009) Changes in cortical dopamine D1 receptor binding associated with cognitive training. Science 323:800–802

    Article  PubMed  CAS  Google Scholar 

  • Miserendino MJ, Haile CN, Kosten TA (2003) Strain differences in response to escapable and inescapable novel environments and their ability to predict amphetamine-induced locomotor activity. Psychopharmacology (Berl) 167:281–290

    CAS  Google Scholar 

  • Murphy CA, Fend M, Russig H, Feldon J (2001) Latent inhibition, but not prepulse inhibition, is reduced during withdrawal from an escalating dosage schedule of amphetamine. Behav Neurosci 115:1247–1256

    Article  PubMed  CAS  Google Scholar 

  • Nestler EJ (2001) Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2:119–128

    Article  PubMed  CAS  Google Scholar 

  • Ortiz J, DeCaprio JL, Kosten TA, Nestler EJ (1995) Strain-selective effects of corticosterone on locomotor sensitization to cocaine and on levels of tyrosine hydroxylase and glucocorticoid receptor in the ventral tegmental area. Neuroscience 67:383–397

    Article  PubMed  CAS  Google Scholar 

  • Pantelis C, Barber FZ, Barnes TR, Nelson HE, Owen AM, Robbins TW (1999) Comparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage. Schizophr Res 37:251–270

    Article  PubMed  CAS  Google Scholar 

  • Pantelis C, Harvey CA, Plant G, Fossey E, Maruff P, Stuart GW, Brewer WJ, Nelson HE, Robbins TW, Barnes TR (2004) Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability. Psychol Med 34:693–703

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Peleg-Raibstein D, Knuesel I, Feldon J (2008) Amphetamine sensitization in rats as an animal model of schizophrenia. Behav Brain Res 191:190–201

    Article  PubMed  CAS  Google Scholar 

  • Peleg-Raibstein D, Sydekum E, Feldon J (2006b) Differential effects on prepulse inhibition of withdrawal from two different repeated administration schedules of amphetamine. Int J Neuropsychopharmacol 9:737–749

    Article  CAS  Google Scholar 

  • Peleg-Raibstein D, Sydekum E, Russig H, Feldon J (2006a) Withdrawal from repeated amphetamine administration leads to disruption of prepulse inhibition but not to disruption of latent inhibition. J Neural Transm 113:1323–1336

    Article  PubMed  CAS  Google Scholar 

  • Peterson JD, Wolf ME, White FJ (2000) Altered responsiveness of medial prefrontal cortex neurons to glutamate and dopamine after withdrawal from repeated amphetamine treatment. Synapse 36:342–344

    Article  PubMed  CAS  Google Scholar 

  • Peterson JD, Wolf ME, White FJ (2006) Repeated amphetamine administration decreases D1 dopamine receptor-mediated inhibition of voltage-gated sodium currents in the prefrontal cortex. J Neurosci 26:3164–3168

    Article  PubMed  CAS  Google Scholar 

  • Pothuizen HH, Neumann KR, Feldon J, Yee BK (2006) Selective nucleus accumbens core lesions enhance dizocilpine-induced but not apomorphine-induced disruption of prepulse inhibition in rats. Behav Pharmacol 17:107–117

    Article  PubMed  Google Scholar 

  • Pryce CR, Lehmann J, Feldon J (1999) Effect of sex on fear conditioning is similar for context and discrete CS in Wistar, Lewis and Fischer rat strains. Pharmacol Biochem Behav 64:753–759

    Article  PubMed  CAS  Google Scholar 

  • Richmond MA, Murphy CA, Pouzet B, Schmid P, Rawlins JN, Feldon J (1998) A computer controlled analysis of freezing behaviour. J Neurosci Methods 86:91–99

    Article  PubMed  CAS  Google Scholar 

  • Rivest S, Rivier C (1994) Stress and interleukin-1 beta-induced activation of c-fos, NGFI-B and CRF gene expression in the hypothalamic PVN: comparison between Sprague–Dawley, Fisher-344 and Lewis rats. J Neuroendocrinol 6:101–117

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 396:157–198

    Article  PubMed  CAS  Google Scholar 

  • Russig H, Durrer A, Yee BK, Murphy CA, Feldon J (2003) The acquisition, retention and reversal of spatial learning in the Morris water maze task following withdrawal from an escalating dosage schedule of amphetamine in Wistar rats. Neuroscience 119:167–179

    Article  PubMed  CAS  Google Scholar 

  • Russig H, Murphy CA, Feldon J (2002) Clozapine and haloperidol reinstate latent inhibition following its disruption during amphetamine withdrawal. Neuropsychopharmacology 26:765–777

    Article  PubMed  CAS  Google Scholar 

  • Russig H, Murphy CA, Feldon J (2005) Behavioural consequences of withdrawal from three different administration schedules of amphetamine. Behav Brain Res 165:26–35

    Article  PubMed  CAS  Google Scholar 

  • Simar MR, Saphier D, Goeders NE (1996) Differential neuroendocrine and behavioral responses to cocaine in Lewis and Fischer rats. Neuroendocrinology 63:93–100

    Article  PubMed  CAS  Google Scholar 

  • Sokolov BP, Polesskaya OO, Uhl GR (2003) Mouse brain gene expression changes after acute and chronic amphetamine. J Neurochem 84:244–252

    Article  PubMed  CAS  Google Scholar 

  • Steckler T, Drinkenburg WH, Sahgal A, Aggleton JP (1998) Recognition memory in rats—II. Neuroanatomical substrates. Prog Neurobiol 54:313–332

    Article  PubMed  CAS  Google Scholar 

  • Stefani MR, Moghaddam B (2002) Effects of repeated treatment with amphetamine or phencyclidine on working memory in the rat. Behav Brain Res 134:267–274

    Article  PubMed  CAS  Google Scholar 

  • Stohr T, Schulte Wermeling D, Szuran T, Pliska V, Domeney A, Welzl H, Weiner I, Feldon J (1998a) Differential effects of prenatal stress in two inbred strains of rats. Pharmacol Biochem Behav 59:799–805

    Article  PubMed  CAS  Google Scholar 

  • Stohr T, Schulte Wermeling D, Weiner I, Feldon J (1998b) Rat strain differences in open-field behavior and the locomotor stimulating and rewarding effects of amphetamine. Pharmacol Biochem Behav 59:813–818

    Article  PubMed  CAS  Google Scholar 

  • Stohr T, Szuran T, Welzl H, Pliska V, Feldon J, Pryce CR (2000) Lewis/Fischer rat strain differences in endocrine and behavioural responses to environmental challenge. Pharmacol Biochem Behav 67:809–819

    Article  PubMed  CAS  Google Scholar 

  • Strecker RE, Eberle WF, Ashby CR Jr (1995) Extracellular dopamine and its metabolites in the nucleus accumbens of Fischer and Lewis rats: basal levels and cocaine-induced changes. Life Sci 56:PL135–PL141

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, Martinez ZA, Hanlon FM, Platten A, Farid M, Auerbach P, Braff DL, Geyer MA (2000) Toward understanding the biology of a complex phenotype: rat strain and substrain differences in the sensorimotor gating-disruptive effects of dopamine agonists. J Neurosci 20:4325–4336

    PubMed  CAS  Google Scholar 

  • Swerdlow NR, Varty GB, Geyer MA (1998) Discrepant findings of clozapine effects on prepulse inhibition of startle: is it the route or the rat? Neuropsychopharmacology 18:50–56

    Article  PubMed  CAS  Google Scholar 

  • Tenn CC, Fletcher PJ, Kapur S (2003) Amphetamine-sensitized animals show a sensorimotor gating and neurochemical abnormality similar to that of schizophrenia. Schizophr Res 64:103–114

    Article  PubMed  Google Scholar 

  • Tenn CC, Kapur S, Fletcher PJ (2005) Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition and latent inhibition. Psychopharmacology (Berl) 180:366–376

    Article  CAS  Google Scholar 

  • van der Staay FJ, Blokland A (1996) Behavioral differences between outbred Wistar, inbred Fischer 344, brown Norway, and hybrid Fischer 344 x brown Norway rats. Physiol Behav 60:97–109

    Article  PubMed  Google Scholar 

  • Varty GB, Geyer MA (1998) Effects of isolation rearing on startle reactivity, habituation, and prepulse inhibition in male Lewis, Sprague–Dawley, and Fischer F344 rats. Behav Neurosci 112:1450–1457

    Article  PubMed  CAS  Google Scholar 

  • Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44:660–669

    PubMed  CAS  Google Scholar 

  • Weinberger DR, Gallhofer B (1997) Cognitive function in schizophrenia. Int Clin Psychopharmacol 12:S29–S36

    Article  PubMed  Google Scholar 

  • Williams GV, Castner SA (2006) Under the curve: critical issues for elucidating D1 receptor function in working memory. Neuroscience 139:263–276

    Article  PubMed  CAS  Google Scholar 

  • Wolf ME (2003) Effects of psychomotor stimulants on glutamate receptor expression. Methods Mol Med 79:13–31

    PubMed  CAS  Google Scholar 

  • Wong DF, Wagner HN Jr, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA, Toung JK, Malat J, Williams JA, O'Tuama LA, Snyder SH, Kuhar MJ, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234:1558–1563

    Article  PubMed  CAS  Google Scholar 

  • Yee BK, Chang DL, Feldon J (2004) The effects of dizocilpine and phencyclidine on prepulse inhibition of the acoustic startle reflex and on prepulse-elicited reactivity in C57BL6 mice. Neuropsychopharmacology 29:1865–1877

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The present study was supported by the Swiss Federal Institute of Technology (ETH) Zurich. The authors are also grateful to Peter Schmid for his excellent technical support, to Tamaki Bieri, Stéphanie McGarrity, Michel Schaffner, Felix Schlegel, Monika Seps, Ronald Vogel, and Tianbuo Yao for technical assistance, and to the animal husbandry staff at the Laboratory of Behavioral Neurobiology for their maintenance of the subjects used in the experiments.

Author information

Authors and Affiliations

  1. Laboratory of Behavioural Neurobiology, Federal Institute of Technology Zurich, Schorenstrasse 16, Schwerzenbach, 8603, Switzerland

    Daria Peleg-Raibstein, Benjamin K. Yee, Joram Feldon & Jonas Hauser

Authors
  1. Daria Peleg-Raibstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benjamin K. Yee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joram Feldon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jonas Hauser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daria Peleg-Raibstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peleg-Raibstein, D., Yee, B.K., Feldon, J. et al. The amphetamine sensitization model of schizophrenia: relevance beyond psychotic symptoms?. Psychopharmacology 206, 603–621 (2009). https://doi.org/10.1007/s00213-009-1514-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-009-1514-7

Keywords

Search

Navigation