Abstract
The number of nerve cells in two different areas of the corpus striatum (i.e., ventrolateral and dorsomedial) was estimated in rat brain after long-term (36 weeks) treatment with the neuroleptic flupenthixol. Nine rats were given weekly injections of 4 mg/kg flupenthixol dissolved in Viscoleo® i.m., and seven rats received Viscoleo® alone. Fourteen to 18 weeks after the last drug injection, the animals were decapitated and half of each brain was fixated with formalin for cellcount analysis and the remaining half used for a biochemical analysis (Nielsen, 1977). Separate cell counts in the ventrolateral and dorsomedial corpus striatum yielded a significant cell loss of approximately 10%, but only in the ventrolateral striatum of treated animals. These results suggest at least one concrete anatomical basis for the behavioral and biochemical deficits found in the same animals, as reported earlier. The results further suggest that persistent irreversible anatomical changes can follow long-term neuroleptic treatment. The inconsistencies of results regarding cell loss in the corpus striatum may be due to neglect of dorsal-ventral structural differences in corpus striatum.
Similar content being viewed by others
References
Bunney, B. S., Aghajanian, G. K.: the precise localization of nigral afferents in the rat as determined by a retrograde tracing technique. Brain Res. 117, 423–435 (1976)
Clavier, R. M., Corcoran, M. E.: Attenuation of self-stimulation from substantia nigra but not dorsal tegmental noradrenergic bundle by lesions of sulcal prefrontal cortex. Brain Res. 113, 59–69 (1976)
Cools, A. R., Struyker Boudier, H. A. J., Van Rossum, J. M.: Dopamine receptors: selective agonists and antagonists of functionally distinct types within the feline brain. Eur. J. Pharmacol. 37, 283–293 (1976)
Divac, I.: Neostriatum and functions of prefrontal cortex. Acta Neurobiol. Exp. 32, 461–477 (1972)
Divac, I.: The mammalian neostriatum: its functional heterogenity associated with topical input from the neocortex. Doctoral dissertation, University of Copenhagen, F. A. D. L. 1977
Fog, R., Pakkenberg, H., Juul, P., Jørgensen, O. S., Andersen, J.: High dose treatment of rats with perphenazine enanthate. Psychopharmacology 50, 305–307 (1977)
Gerlach, J., Reisby, N., Randrup, A.: Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia (Berl.) 34, 21–35 (1974)
Gerlach, J.: Long-term effect of perphenazine on the substantia nigra in rats. Psychopharmacologia (Berl.) 45, 51–54 (1975)
Gerlach, J., Thorsen, K.: The movement pattern of oral tardive dyskinesia in relation to anticholinergic antidopaminergic treatment. Int. Pharmacopsychiatry 11, 1–7 (1976)
Gerlach, J.: Relationship between tardive dyskinesia, L-dopa-induced hyperkinesia and parkinsonism. Psychopharmacology 51, 259–263 (1977)
Gross, H., Kaltenbäck, E.: Neuropathological findings in persistent hyperkinesia after neuroleptic long-term therapy. In: The present status of psychotropic drugs, A. Cerletti and F. J. Bové, eds. Amsterdam: Excerpta Medica 1968
Iversen, L. L., Rogawski, M. A., Miller, R. J.: Comparison of the effects of neuroleptic drugs on pre- and post-synaptic dopaminergic mechanisms in the rat striatum. Mol. Pharmacol. 12, 251–262 (1976)
Klawans, H. L.: The pharmacology of extrapyramidal movement disorder. Basel: Karger 1973
Knook, H. L.: The fibre-connections of the forebrain. Assen, Holland: Van Gorcum 1965
König, J. F. R., Klippel, R. A.: The rat brain: a stereotaxic atlas. Baltimore, Md.: Williams and Wilkins 1963
Leonard, C. M.: The prefrontal cortex of the rat. I. Cortical projection of the medio dorsal nucleus. II. Efferent connections. Brain Res. 12, 321–343 (1969)
Livesey, P. J., Muter, V.: Functional differentiation within the neostriatum of the rat using electrical (blocking) stimulation during discrimination learning. J. Comp. Physiol. Psychol. 90, 203–211 (1976)
Lyon, M.: Rostral forebrain lesions in relation to central stimulant and neuroleptic drug action. C.I.N.P. Congress, Paris, 1974. J. Pharmacol. (Suppl. 2) 5, 61–62 (1974)
Neill, D. B., Boggan, W. O., Grossman, S. P.: Behavioral effects of amphetamine in rats with lesions in the corpus striatum. J. Comp. Physiol. Psychol. 89, 1019–1030 (1974a)
Neill, D. B., Ross, J. F., Grossman, S. P.: Effects of lesions in the dorsal or ventral striatum on locomotor activity and on locomotor effects of amphetamine. Pharmacol. Biochem. Behav. 2, 697–702 (1974b)
Neill, D. B., Linn, C. L.: Deficits in consummatory responses to regulatory challenges following basal ganglia lesions in rats. Physiol. Behav. 14, 617–624 (1975)
Nielsen, E. B.: Long-term behavioral and biochemical effects following prolonged treatment with a neuroleptic drug (Flupenthixol) in rats. Psychopharmcology 54, 203–208 (1977)
Pakkenberg, H., Fog, R., Nilakantan, B.: The long-term effect of perphenazine enanthate on the rat brain. Some metabolic and anatomical findings. Psychopharmacologia (Berl.) 29, 329–336 (1973)
Pakkenberg, H., Fog, R.: Short-term effect of perphenazine enanthate on the rat brain. Psychopharmacologia (Berl.) 40, 165–169 (1974)
Weiss, B., Santelli, S., Lusink, G.: Movement disorders induced in monkeys by chronic haloperidol treatment. Psychopharmacology 53, 289–293 (1977)
Winocur, G.: Functional dissociation within the caudate nucleus of rats. J. Comp. Physiol. Psychol. 86, 432–439 (1974)
Woolsey, C. N.: The somatotopic organization of the cortex. In: Biological and biochemical bases of behavior, H. Harlow and C. N. Woolsey, Eds. Madison: University of Wisconsin 1958
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nielsen, E.B., Lyon, M. Evidence for cell loss in corpus striatum after long-term treatment with a neuroleptic drug (flupenthixol) in rats. Psychopharmacology 59, 85–89 (1978). https://doi.org/10.1007/BF00428036
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00428036