Abstract
The acute and chronic administration effects of risperidone (Ris), a mixed 5HT2/D2 receptor antagonist, versus haloperidol (Hal) on dopaminergic and serotoninergic activity were investigated in the rat prefrontal cortex (Pfc), and the whole striatum (Str) as well as separately, in dorsal striatum (StrD) and nucleus accumbens (Acb). During acute administration, Hal was found to be more potent than Ris in increasing DA turnover rate in StrD. In contrast, during chronic administration, Ris but not Hal, continued to increase DA turnover activity in StrD. Moreover, in contrast to Hal, chronic Ris treatment continued to increase DA and 5-HT turnover rate in Pfc. These differential effects reveal that Hal does not share common characteristics with Ris with respect to its neurochemical profile in the Str and Pfc.
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Anden NE, Grenhoff J, Svensson TH (1988) Does treatment with haloperidol for 3 weeks produce depolarization block in midbrain dopamine neurons of unanaesthetized rats. Psychopharmacology 96:558–560
Arnt J (1982) Pharmacological specificity of conditioned avoidance responce inhibition in rats: inhibition by neuroleptics and correlation to dopamine receptor blockade. Acta Pharmacolo Toxicol 51:321
Bacopoulos NC, Spokes EG, Bird ED, Roth RH (1979) Antipsychotic drug action in schizophrenic patients: effects on cortical dopamine metabolism after long-term treatment. Science 205:1405–1407
Bannon MJ, Roth RH (1983) Pharmacology of mesocortical dopamine neurons. Pharmacol Rev 35 [1]:53–68
Blaha CD, Lane RF (1984) Direct in vivo electrochemical monitoring of dopamine release in response to neuroleptic drugs. Eur J Pharmacol 98:113–119
Blaha CD, Lane FR (1987) Chronic treatment with classical and atypical antipsychotic drugs differentially decreases dopamine release in striatum and n. accumbens in vivo. Neurosci Lett 78:199–204
Bowers MB Hoffman FJ (1986) Homovanillic acid in caudate and prefrontal cortex following acute and chronic neuroleptic administration. Psychopharmacology 88:63–65
Bunney BS, Chiodo LA (1984) Mesocortical dopamine systems: further electrophysiological and pharmacological characteristics. In: Monoamine innervation of cerebral cortex. Alan R. Liss, New York, pp 263–277
Carli M, Jones G.H, Robbins TW (1989) Effects of unilateral dorsal and ventral striatal dopamine derlation on visual neglect in the rat: a neural and behavioural analysis. Neuroscience 29 [2]:309–327
Chen J, Paredes W, Gardner EL (1991) Chronic treatment with clozapine selectively decreases basal dopamine release in n. accumbens but not in caudate-putamen as measured by in vivo brain microdialysis: further evidence for depolarization block. Neurosci Lett 122:127–131
Chiodo LA, Bunney BS (1983) Typical and atypical neuroleptics: differential effect of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons. J Neurosci 3:1607–1619
Chouinard G, Arnott W (1993) Clinical revew of risperidone. Can J Psychol 38 [Suppl. 3]:89–95
Cooper JR, Bloom FE, Roth RH (1991) The biochemical basis of neuropharmacology, 6th edn. Oxford University Press, Oxford
Costall B, Naylor RJ (1976) A comparizon of the abilities of typical neuroleptic agents and of thioridazine, clozapine, sulpiride and metoclopramide to antagonize the hyperactivity induced by dopamine applied intracerebrally to areas of the extrapyramidal and mesolimbic systems. Eur J Pharmacol 40:9
Deutch AY (1992) The regulation of subcortical dopamine systems by the prefrontal cortex: interactions of central dopamine systems and the pathogenesis of schizophrenia. J Neural Transm 36:61–89
Di Giulio AM, Groppettia A, Cattabeni F, Galli CL, Maggi A, Algeri S, Ponzio F (1978) Significance of dopamine metabolites in the evaluation of drugs acting on dopaminergic neurons. Eur J Pharmacol 52:201–207
Ereshefsky L, Lacombe S (1993) Pharmacological profile of risperidone. Can J Psychiatry 38 [Suppl. 3]:80–88
Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizoprenia. Neuroscience 41[1]:1–24
Grace AA (1992) The depolarization block hypothesis of neuroleptic action implications for the etiology and treatment of schizophrenia. J Neural Transm 36:91–131
Grace AA (1993) Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia. J Neural Transm 91:111–134
Hernandez L, Hoebel BG (1989) Haloperidol given chronically decreases basal dopamine in the prefrontal cortex more than the striatum or nucleus accumbens as simultaneously measured by microdialysis. Brain Res Bull 22:763–769
Ichikawa J, Meltzer HY (1991) Differential effects of repeated treatment with haloperidol and clozapine on dopamine release and metabolism in the striatum and nucleus accumbens. J Pharmacol Exp Ther 256:348–357
Imperato A, Di Chiara G (1985) Dopamine release and metabolism in awake rats after systemic neuroleptics as studied by trans-striatal dialysis. J Neurosci 5:297–306
Lane R, Blaha C, Rivet JM (1988) Selective inhibition of mesolimbic dopamine release following chronic administration of clozapine: involvement of α1-noradrenergic receptors demonstrated by in vivo voltammetry. Brain Res 460:398–401
Learner, P, Nose P (1977) Haloperidol: effect of long-term treatment on rat striatal dopamine synthesis and turnover. Science 19:181–183
Leysen JE, Gommeren W, Eens A, Chaffoy de Courcelles D, Stoof JC, Janssen PAJ (1988) Biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther 247:661–670
Leysen JE, Janssen PMF, Gommeren W, Wynants J, Pauwels P, Janssen PAJ (1991) In vitro and in vivo receptor binding and effects on monoamine turnover in rat brain regions of the novel antipsychotics risperidone and ocaperidone. Mol Pharmacol 41:494–508
Leysen JE, Janssen PMF, Schotte A, Luyten W, Megens A (1993) Interaction of antipsychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical effects: role of 5-HT2 receptors. Psychopharmacology 112:s40-s54
Mefford IN, Roth KA, Agren H, Barchas JD (1988) Enhancement of dopamine metabolism in rat brain frontal cortex: a common effect of chronically administered antipsychotic drugs. Brain Res 475:380–384
Meltzer HY (1991) The mechanism of action of novel antipsychotic drugs. Schizophr Bull 17 [2]:263–287
Nomikos GG, Iurlo M, Anderson JL, Kimura K, Svensson TH (1994) Systemic administration of amperozide, a new atypical antipsychotic drug, preferentially increases dopamine release in the rat medial prefrontal cortex. Psychopharmacology 115:147–156
Nomikos GG, Hertel P, Markus M, Iurlo M, Svensson TH (1995) Selective action of risperidone on serotonin but not dopamine metabolism in the rat prefrontal cortex. Workshop: critical issues in the treatment of schizophrenia — campaign on schizophrena. Abstract book, pp 183–184
Pehek EA, Meltzer HY, Yamamoto BK (1993a) Local administration of ritanserin or ICS 205,930 enhances dopamine and serotonin efflux in rat prefrontal cortex. Soc Neurosci Abstr 19:302
Pehek EA, Meltzer HY, Yamamoto BK (1993b) The atypical antipsychotic drug amperozide enhances rat cortical and striatal dopamine efflux. Eur J Pharmacol 240:107–111
Reynolds, GP (1992) Developments in the drug treatment of schizophrenia. Trends Pharmocol Sci 13:116–121
Roth RH (1983) Neuroleptics: functional neurochemistry. In: Coyle JT, Enna SJ (eds) Neuroleptics: neurochemical, behavioral and clinical perspectives. Raven, New York, pp 119–156
Schmidt CJ, Fadayel GN (1995) The selective 5-HT2A receptor antagonist, MDL 100,907, increases dopamine efflux in the prefrontal cortex of the rat. Eur J Pharmacol 273:273–279
Schotte A, Janssen PFM, Megens AAHP, Leysen JE (1993) Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidole, measured ex vivo by quantitative autoradiography. Brain Res 631:191–202
Seeman P (1995) Dopamine receptors. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: the fourth generation of progress. Raven Press, New York
Sharp T, Zetterstrom T, Series HG, Carlsson A, Graham E, Smith DG, Ungerstedt U (1987) HPLC-EC analysis of catechols and indoles in rat brain dialysates. Life Sci 41:869–872
Skarsfelt T (1988) Differential effects after repeated treatment with haloperidol, lozapine, thioridazine and tefludazine on SNc and VTA dopamine neurons in rats. Life Sci 42:1037–1044
Snyder SH, Banerjee SP, Yamamura HI, Greenberg D (1974) Drugs neurotransmitters and schizophrenia. Science 184:1243–1253
Westerink BHC (1979) The effects of drugs on dopamine biosynthesis and metabolism in the brain. In: Horn AS, Korf J, Westering BHS (eds) The neurobiology of dopamine. Academic Press, London, pp 251–290
White FJ, Wang RY (1983) Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine neurons. Science 221:1054–1057
White FJ Wang RY (1982) Comparison of the effects of chronic haloperidol treatment on A9 and A10 dopamine neurons in the rat. Life Sci 32:983–993
Zetterstrom T, Sharp T, Ugerstedt U (1985) Effect of neuroleptic drugs on striatal dopamine release and metabolism in the awake rat studied by intracerebral dialysis. Eur J Pharmacol 106:27–37
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Stathis, P., Antoniou, K., Papadopoulou-Daifotis, Z. et al. Risperidone: a novel antipsychotic with many “atypical” properties?. Psychopharmacology 127, 181–186 (1996). https://doi.org/10.1007/BF02246125
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DOI: https://doi.org/10.1007/BF02246125