Download PDF
Pharmacopsychiatry 2016; 49(02): 62-65
DOI: 10.1055/s-0035-1569417
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Concurrent Risperidone Administration Attenuates the Development of Locomotor Sensitization Following Sub-Chronic Phencyclidine in Rats

C. E. McKibben
1   Division of Psychiatry and Neuroscience, Queen’s University Belfast, Northern Ireland, United Kingdom
,
G. P. Reynolds
1   Division of Psychiatry and Neuroscience, Queen’s University Belfast, Northern Ireland, United Kingdom
2   Biomedical Research Centre, Sheffield Hallam University, United Kingdom
,
T. A. Jenkins
1   Division of Psychiatry and Neuroscience, Queen’s University Belfast, Northern Ireland, United Kingdom
3   School of Medical Sciences, Health Innovations Research Institute, RMIT University, Victoria, Australia
› Author Affiliations
Further Information

Publication History

received 29 July 2015
revised 29 November 2015

accepted 06 January 2016

Publication Date:
02 February 2016 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction: In schizophrenia early treatment may prevent disorder onset, or at least minimize its impact, suggesting possible neuroprotective properties of antipsychotics. The present study investigates the effects of chronic treatment with the atypical antipsychotic, risperidone, on locomotor sensitization in the subchronic phencyclidine-treated rat.

Methods: Rats were treated with phencyclidine sub-chronically (2 mg/kg bi-daily for one week followed by a one-week wash-out period) or vehicle. Half of the phencyclidine group was concurrently treated with risperidone (0.5 mg/kg IP) twice daily for 15 days, beginning 3 days before the start of phencyclidine administration. 6 weeks after treatment all rats were injected with a phencyclidine-challenge (3.2 mg/kg) and immediately after their locomotor activity measured for 20 min.

Results: Co-administration of risperidone at the time of phencyclidine administration significantly reduced the phencyclidine-challenge locomotor effect administered 6 weeks later.

Discussion: These results demonstrate that concurrent risperidone is neuroprotective, and clearly suggests its functionality can be translated to a clinical setting for treating the so-called prodrome.

Key words

animal models - schizophrenia - risperidone (risperdal)
 

  • References

  • 1 Perkins DO, Gu HB, Boteva K et al. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: A critical review and meta-analysis. Am J Psychiatry 2005; 162: 1785-1804
    CrossrefPubMedSearch in Google Scholar
  • 2 Leucht S, Busch R, Hamann J et al. Early-onset hypothesis of antipsychotic drug action: A hypothesis tested, confirmed and extended. Biol Psychiatry 2005; 57: 1543-1549
    CrossrefPubMedSearch in Google Scholar
  • 3 Massana G, Salgado-Pineda P, Junque C et al. Volume changes in gray matter in first-episode neuroleptic-naive schizophrenic patients treated with risperidone. J Clin Psychopharmacol 2005; 25: 111-117
    CrossrefPubMedSearch in Google Scholar
  • 4 Molina V, Reig S, Sanz J et al. Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia. Schizophr Res 2005; 80: 61-71
    CrossrefPubMedSearch in Google Scholar
  • 5 Liddle PF, Lane CJ, Ngan ET. Immediate effects of risperidone on cortico-striato-thalamic loops and the hippocampus. Br J Psychiatry 2000; 177: 402-407
    CrossrefPubMedSearch in Google Scholar
  • 6 McGorry PD, Yung AR, Phillips LJ et al. Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry 2002; 59: 921-928
    Search in Google Scholar
  • 7 McGorry PD, Nelson B, Phillips LJ et al. Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: twelve-month outcome. J Clin Psychiatry 2013; 74: 349-356
    CrossrefPubMedSearch in Google Scholar
  • 8 Jenkins TA, Harte MK, McKibben CE et al. Disturbances in social interaction occur along with pathophysiological deficits following sub-chronic phencyclidine administration in the rat. Behav Brain Res 2008; 194: 230-235
    CrossrefPubMedSearch in Google Scholar
  • 9 McKibben CE, Reynolds GP, Jenkins TA. Analysis of sociability and preference for social novelty in the acute and subchronic phencyclidine rat. J Psychopharmacol 2014; 28: 955-963
    CrossrefPubMedSearch in Google Scholar
  • 10 Snigdha S, Neill JC. Efficacy of antipsychotics to reverse phencyclidine-induced social interaction deficits in female rats – A preliminary investigation. Behav Brain Res 2008; 187: 489-494
    CrossrefPubMedSearch in Google Scholar
  • 11 Spielewoy C, Markou A. Withdrawal from chronic phencyclidine treatment induces long-lasting depression in brain reward function. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 2003; 28: 1106-1116
    PubMedSearch in Google Scholar
  • 12 Baird JP, Turgeon S, Wallman A et al. Behavioral processes mediating phencyclidine-induced decreases in voluntary sucrose consumption. Pharmacol Biochem Behav 2008; 88: 272-279
    CrossrefPubMedSearch in Google Scholar
  • 13 McKibben CE, Jenkins TA, Adams HN et al. Effect of pretreatment with risperidone on phencyclidine-induced disruptions in object recognition memory and prefrontal cortex parvalbumin immunoreactivity in the rat. Behav Brain Res 2010; 208: 132-136
    CrossrefPubMedSearch in Google Scholar
  • 14 Abdul-Monim Z, Neill JC, Reynolds GP. Sub-chronic psychotomimetic phencyclidine induces deficits in reversal learning and alterations in parvalbumin-immunoreactive expression in the rat. J Psychopharmacol 2007; 21: 198-205
    CrossrefPubMedSearch in Google Scholar
  • 15 Grayson B, Idris NF, Neill JC. Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat. Behav Brain Res 2007; 184: 31-38
    CrossrefPubMedSearch in Google Scholar
  • 16 Rodefer JS, Murphy ER, Baxter MG. PDE10A inhibition reverses subchronic PCP-induced deficits in attentional set-shifting in rats. Eur J Neurosci 2005; 21: 1070-1076
    CrossrefPubMedSearch in Google Scholar
  • 17 van den Buuse M. Modeling the positive symptoms of schizophrenia in genetically modified mice: pharmacology and methodology aspects. Schizophr Bull 2010; 36: 246-270
    CrossrefPubMedSearch in Google Scholar
  • 18 Sturgeon RD, Fessler RG, Meltzer HY. Behavioral rating scales for assessing phencyclidine-induced locomotor activity, stereotyped behavior and ataxia in rats. Eur J Pharmacol 1979; 59: 169-179
    CrossrefPubMedSearch in Google Scholar
  • 19 Nabeshima T, Fukaya H, Yamaguchi K et al. Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine. Eur J Pharmacol 1987; 135: 23-33
    CrossrefPubMedSearch in Google Scholar
  • 20 McLean S, Woolley M, Neill J. Effects of subchronic phencyclidine on behaviour of female rats on the elevated plus maze and open field. J Psychopharmacol (Oxford, England) 2009; 24: 787-790
    PubMedSearch in Google Scholar
  • 21 Xu X, Domino EF. Phencyclidine-induced behavioral sensitization. Pharmacol Biochem Behav 1994; 47: 603-608
    CrossrefPubMedSearch in Google Scholar
  • 22 Johnson KM, Phillips M, Wang C et al. Chronic phencyclidine induces behavioral sensitization and apoptotic cell death in the olfactory and piriform cortex. J Neurosci Res 1998; 52: 709-722
    CrossrefPubMedSearch in Google Scholar
  • 23 Phillips M, Wang C, Johnson KM. Pharmacological characterization of locomotor sensitization induced by chronic phencyclidine administration. J Pharmacol Exp Ther 2001; 296: 905-913
    PubMedSearch in Google Scholar
  • 24 Jenkins TA, Harte MK, Reynolds GP. Effect of subchronic phencyclidine administration on sucrose preference and hippocampal parvalbumin immunoreactivity in the rat. Neurosci Lett 2010; 471: 144-147
    CrossrefPubMedSearch in Google Scholar
  • 25 Li M, He E, Volf N. Time course of the attenuation effect of repeated antipsychotic treatment on prepulse inhibition disruption induced by repeated phencyclidine treatment. Pharmacol Biochem Behav 2011; 98: 559-569
    CrossrefPubMedSearch in Google Scholar
  • 26 Qiao J, Zhang QL, Li M. Long-term impacts of adolescent risperidone treatment on behavioral responsiveness to olanzapine and clozapine in adulthood. Prog Neuropsychopharmacol Biol Psychiatry 2014; 48: 177-185
    CrossrefPubMedSearch in Google Scholar
  • 27 Stewart J, Badiani A. Tolerance and sensitization to the behavioral effects of drugs. Behav Pharmacol 1993; 4: 289-312
    PubMedSearch in Google Scholar
  • 28 Steketee JD, Kalivas PW. Drug wanting: behavioral sensitization and relapse to drug-seeking behavior. Pharmacol Rev 2011; 63: 348-365
    CrossrefPubMedSearch in Google Scholar
  • 29 Kalinichev M, Bate ST, Jones DN. Models of aspects of schizophrenia: behavioral sensitization induced by subchronic phencyclidine administration. Curr Protoc Pharmacol 2009; Chapter 5: Unit 5 54
    PubMedSearch in Google Scholar
  • 30 Kitaichi K, Yamada K, Yoneda Y et al. Risperidone prevents the development of supersensitivity, but not tolerance, to phencyclidine in rats treated with subacute phencyclidine. Life Sci 1995; 56: 531-543
    CrossrefPubMedSearch in Google Scholar
  • 31 Balla A, Sershen H, Serra M et al. Subchronic continuous phencyclidine administration potentiates amphetamine-induced frontal cortex dopamine release. Neuropsychopharmacology 2003; 28: 34-44
    CrossrefPubMedSearch in Google Scholar
  • 32 Yan BC, Park JH, Ahn JH et al. Neuroprotection of posttreatment with risperidone, an atypical antipsychotic drug, in rat and gerbil models of ischemic stroke and the maintenance of antioxidants in a gerbil model of ischemic stroke. J Neurosci Res 2014; 92: 795-807
    CrossrefPubMedSearch in Google Scholar
  • 33 Yulug B, Yildiz A, Guzel O et al. Risperidone attenuates brain damage after focal cerebral ischemia in vivo. Brain Res Bull 2006; 69: 656-659
    CrossrefPubMedSearch in Google Scholar
  • 34 Stojkovic T, Radonjic NV, Velimirovic M et al. Risperidone reverses phencyclidine induced decrease in glutathione levels and alterations of antioxidant defense in rat brain. Prog Neuropsychopharmacol Biol Psychiatry 2012; 39: 192-199
    CrossrefPubMedSearch in Google Scholar
  • 35 Petronijevic N, Sopta J, Doknic M et al. Chronic risperidone exposure does not show any evidence of bone mass deterioration in animal model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2013; 46: 58-63
    CrossrefPubMedSearch in Google Scholar
  • 36 Wang HD, Deutch AY. Dopamine depletion of the prefrontal cortex induces dendritic spine loss: reversal by atypical antipsychotic drug treatment. Neuropsychopharmacol 2008; 33: 1276-1286
    CrossrefPubMedSearch in Google Scholar
  • 37 Li XM, Chlan-Fourney J, Juorio AV et al. Differential effects of olanzapine on the gene expression of superoxide dismutase and the low affinity nerve growth factor receptor. J Neurosci Res 1999; 56: 72-75
    CrossrefPubMedSearch in Google Scholar
  • 38 Ukai W, Ozawa H, Tateno M et al. Neurotoxic potential of haloperidol in comparison with risperidone: implication of Akt-mediated signal changes by haloperidol. J Neural Transm 2004; 111: 667-681
    CrossrefPubMedSearch in Google Scholar
  • 39 Gasso P, Mas S, Molina O et al. Neurotoxic/neuroprotective activity of haloperidol, risperidone and paliperidone in neuroblastoma cells. Prog Neuropsychopharmacol Biol Psychiatry 2012; 36: 71-77
    CrossrefPubMedSearch in Google Scholar
  • 40 Jenkins TA, Elliott JJ, Ardis TC et al. Tryptophan depletion impairs object-recognition memory in the rat: Reversal by risperidone. Behav Brain Res 2009; 208: 479-483
    PubMedSearch in Google Scholar
  • 41 Goodman LS, Brunton LL, Chabner B et al. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011
    Search in Google Scholar