Abstract
Cebus apella monkeys were chronically administered the antipsychotic drug fluphenazine decanoate for periods ranging from 3.5 to 5.5 years. In the present study, four of these monkeys and two controls were tested for cognitive abilities on a spatial learning task, which consisted of an original discrimination and four reversals of that discrimination. No effect of fluphenazine administration was seen in the rate of learning the original discrimination, but the carryover of learning across discrimination reversals was significantly reduced by fluphenazine. After overtraining on the original discrimination, the controls showed the normal difficulty in learning the first reversal. The fluphenazine-treated monkeys showed no such disruption. On subsequent reversals, the controls showed continually improving performance, so that on the third and fourth reversals they had near-perfect scores. On the other hand, the fluphenazine-treated monkeys showed no change over the four reversals. Unlike normal monkeys, their learning did not improve with practice. Although simple forms of learning seem to be relatively unaffected by chronic fluphenazine administration, more complex learning is disrupted.
Similar content being viewed by others
References
Asarnow RF, MacCrimmon DJ (1978) Residual performance deficit in clinically remitted schizophrenics: a marker for schizophrenia? J Abnorm Psychol 87:597–608.
Asarnow RF, MacCrimmon DJ (1981) Span of apprehension deficits during the postpsychotic stages of schizophrenica: a replication and extension. Arch Gen Psychiatry 38:1006–1011.
Bárány S, Ingvast A, Gunne LM (1979) Development of acute dystonia and tardive dyskinesia in cebus monkeys. Res Commun Chem Pathol Pharmacol 25:269–279.
Beatty WW, Rush JR (1983) Spatial working memory: effects of monoaminergic antagonists. Pharmacol Biochem Behav 18:7–12.
Brozoski TJ, Brown RM, Rosvold HE, Goldman PS (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205:929–931.
Bushnell PJ, Bowman RE (1979) Reversal learning deficits in young monkeys exposed to lead. Pharmacol Biochem Behav 10:733–742.
Erickson WD, Yellin AM, Hopwood JH, Realmuto GM, Greenberg LM (1984) The effects of neuroleptics on attention in adolescent schizophrenics. Biol Psychiatry 19:745–753.
Famuyiwa OO, Eccleston D, Donaldson AA (1979) Tardive dyskinesia and dementia. Br J Psychiatry 135:500–504.
Glassman RB, Glassman HN (1980) Oral dyskinesia in brain-damaged rats withdrawn from a neuroleptic: implications for models of tardive dyskinesia. Psychopharmacology 69:19.
Goldberg E (1985) Akinesia tardive dysmentia and frontal lobe disorder in schizophrenia. Schizophr Bull 11:255–263.
Goldstone S, Lhamon WT (1976) The effects of haloperidol upon temporal information processing by patients with Tourette's syndrome. Psychopharmacology 50:7–10.
Goldstone S, Nurnberg HG, Lhamon WT (1979) Effects of trifluoperazine, chlorpromazine and haloperidol upon temporal information processing by schizophrenic patients. Psychopharmacology 65:119–124.
Gunne LM, Bárány S (1976) Haloperidol-induced tardive dyskinesia in monkeys. Psychopharmacology 50:237–240.
Gunne LM, Growdon J, Glaeser B (1982) Oral dyskinesia in rats following brain lesions and neuroleptic drug administration. Psychopharmacology 77:134–139.
Gunne LM, Häggström JE, Sjoquist B (1984) Association with persistent neuroleptic-induced dyskinesia of regional changes in brain GABA synthesis. Nature 309:347–349.
Harlow HF, Bromer JA (1938) A test apparatus for monkeys. Psychol Rep 2:434–436.
Keppel G (1982) Design and analysis: a researcher's handbook, 2nd edn. Prentice-Hall, Englewood Cliffs, NJ
Lehmann HE (1979) Negative effects of psychotherapeutic drug treatment. Prog Neuropsychopharmacol 3:223–229.
Levin ED, Johansson P (1988) Cognitive effects of long-term chronic neuroleptic drug administration. Toxicologist 8:77.
Levin ED, Galen D, Ellison GD (1987) Chronic haloperidol effects on radial-arm maze performance and oral movements in rats. Pharmacol Biochem Behav 26:1–6.
Oades RD (1981) Impairments of search behavior in rats after haloperidol treatment, hippocampal or neocortical damage suggest a mesocortical limbic role in cognition. Biol Psychol 12:77–85.
Oades RD (1982) Attention and schizophrenia: neurological bases. Pitman, Boston
Oberg R, Divac I (1979) “Cognitive” function of the neostriatum. In: Divac I, Oberg R (eds) The neostriatum. Pergamon Press, New York
Platt JE, Campbell M, Grega DM, Green WH (1984) Cognitive effects of haloperidol and lithium in aggressive conduct-disorder children. Psychopharmacol Bull 20:93–97.
Simon H, Scatton S, LeMoal M (1980) Dopaminergic A10 neurons are involved in cognitive functions. Nature 286:150–151.
Spohn HE, Coyne L, Lacoursiere R, Mazur D, Hayes K (1985) Relation of neuroleptic dose and tardive dyskinesia to attention, information-processing and psychophysiology in medicated schizophrenics. Arch Gen Psychiatry 42:849–859.
Struve FA, Willner AE (1983) Cognitive dysfunction and tardive dyskinesia. Br J Psychiatry 143:597–600.
Waddington JL (1987) Tardive dyskinesia in schizophrenia and other disorders: Associations with ageing, cognitive dysfunction and structural brain pathology in relation to neuroleptic exposure. Hum Psychopharmacol 2:11–22.
Waddington JL, Youssef HA (1986a) An unusual cluster of tardive dyskinesia in schizophrenia: association with cognitive dysfunction and negative symptoms. Am J Psychiatry 143:1162–1165.
Waddington JL, Youssef HA (1986b) Late onset involuntary movements in chronic schizophrenia: relationship of tardive dyskinesia to intellectual impairment and negative symptoms rather than to raised exposure to neuroleptics or anticholinergics. Br J Psychiatry 149:616–620.
Waddington JL, Youssef HA, Malloy AG, O'Boyle KM, Pugh MT (1985) Association of intellectual impairment, negative symptoms and aging with tardive dyskinesia. J Clin Psychiatry 46:29–33.
Waddington JL, Youssef HA, Dolphin C, Kinsella A (1987) Cognitive dysfunction, negative symptoms, and tardive dyskinesia in schizophrenia. Arch Gen Psychiatry 44:907–912.
Wade JB, Lehman L, Hart RP, Linden D, Novak T (1987) Tardive dyskinesia and cognitive impairment. International Neuropsychological Society Conference, 15th Annual, Washington, DC
Wegner JT, Catalano R, Gibralter J, Kane JM (1985a) Schizophrenics with tardive dyskinesia: neuropsychological deficit and family psychopathology. Arch Gen Psychiatry 42:860–865.
Wegner JT, Kane JM, Weinhold P, Woerner M, Kino B, Lieberman J (1985b) Coghitive impairment in tardive dyskinesia. Psychiatry Res 16:351–337.
Wolfe ME, Ryan JJ, Mosnaim AD (1983) Cognitive function in tardive dyskinesia. Psychol Med 13:671–674.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Levin, E.D., Gunne, L.M. Chronic neuroleptic effects on spatial reversal learning in monkeys. Psychopharmacology 97, 496–500 (1989). https://doi.org/10.1007/BF00439554
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00439554