Summary
Post-mortem brain regions of schizophrenics were investigated in comparison to matched controls regarding synaptosomal K+-stimulated [3H]DA release and its modulation by DA autoreceptors. Brain specimens were cryopreserved in liquid nitrogen until release experiments; synaptosomes from brain pieces preincubated with dimethylsulfoxide have unchanged ability for [3H]DA release and its autoreceptor-mediated inhibition after cryo-preservation. Release data were individually corrected for post-mortem delay back to the zero-time state based on [3H]DA release alterations after in situ preservation of rat heads.
In schizophrenia, the K+-stimulated [3H]DA release from superfused synaptosomes of the nucleus (n.) accumbens and n. caudatus was diminished significantly. Furthermore, functional supersensitivity of the modulatory DA autoreceptors could be demonstrated in these regions. The alterations demonstrated seem not to be due primarily to medication since in neuroleptic-free patients similar changes were shown.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Argiolas A, Fadda F, Melis MR, Marcou M, Porceddu ML, Gessa GL (1982) Delayed inhibition of dopamine synthesis by gamma-butyrolactone and baclofen: dopamine autoreceptor supersensitivity? Eur J Pharmacol 85: 23–27
Breese GR, Baumeister AA, McCown TJ, Emerick SG, Frye GD, Crotty K, Mueller RA (1984) Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats of dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine. J Pharmacol Exp Ther 231: 343–354
Crow TJ (1982) Two dimensions of pathology in schizophrenia: dopaminergic and non-dopaminergic. Psychopharmacol Bull 18: 22–29
Cubeddu LX, Hoffmann IS, James MK, Niedzwiecki DM (1983) Changes in the sensitivity to apomorphine of dopamine receptors modulating dopamine and acetylcholine release after chronic treatment with bromocriptine or haloperidol. J Pharmacol Exp Ther 226: 680–685
Farde L, Wiesel F-A, Hall H, Halldin C, Stone-Elander S, Sedvall G (1987) No D-2 receptor increase in PET study of schizophrenia. Arch Gen Psychiatry 44: 671–672
Fülgraff G, Palm D (1982) Pharmakotherapie und klinische Pharmakologie. Fischer, Stuttgart New York, p 220
Haberland N, Hetey L (1987 a) Studies in post-mortem dopamine uptake. I. Kinetic characterization of the synaptosomal dopamine uptake in rat and human brain after postmortem storage and cryopreservation. Comparison with noradrenaline and serotonin uptake. J Neural Transm 68: 289–301
Haberland N, Hetey L (1987 b) Studies in post-mortem dopamine uptake. II. Alterations of the synaptosomal catecholamine uptake in post-mortem brain regions in schizophrenia. J Neural Transm 68: 303–313
Hetey L, Drescher K (1986) Influence of antipsychotics on presynaptic receptors modulating the release of dopamine in synaptosomes of the nucleus accumbens of rats. Neuropharmacology 25: 1103–1109
Hetey L, Haberland N, Schwitzkowsky R (1985) Study of the synaptosomal catecholamine uptake in post-mortem brain of schizophrenics. In: Boulton AA, Bieck PR, Maitre L, Riederer P (eds) Neuropsychopharmacology of the trace amines: experimental and clinical aspects. Proceedings of the symposium, Tübingen 1985. Humana, Clifton, pp 461–468
Hetey L, Berg R, Schlesinger T (1987) Characterization of synaptosomal dopamine uptake in post-mortem brain regions of schizophrenics. Neurochem Pathol 7: 221–232
Hetey L, Schwitzkowsky R, Haberland N, Ott T (1988) Functional markers of dopaminergic transmission in post-mortem brain in schizophrenia. In: Beart PM, Woodruff GN, Jackson DM (eds) Pharmacology and functional regulation of dopaminergic neurons. Proceedings of the Symposium, Hunter Valley, 1987. Macmillan Press, Basingstoke London, pp 374–376
Meltzer HY (1987) Biological studies in schizophrenia. Schizophr Bull 13: 77–111
Nowak JZ, Arbilla S, Galzin AM, Langer SZ (1983) Changes in sensitivity of release modulating dopamine autoreceptors after chronic treatment with haloperidol. J Pharmacol Exp Ther 226: 558–564
Reynolds GP (1983) Increased concentrations and lateral assymetry of amygdala dopamine in schizophrenia. Nature 305: 527–529
Rodnight R (1983) Schizophrenia: some current neurochemical approaches. J Neurochem 41: 12–21
Schneider K (1959) Clinical psychopathology. Grune and Stratton, New York
Schwitzkowsky R, Hetey L (1989) Characterization of synaptosomal dopamine release in rat and human brain after post-mortem storage and cryopreservation. Neurochem Int 15: 349–354
Spokes EGS, Koch DJ (1978) Post-mortem stability of dopamine, glutamate decarboxylase and choline acetyltransferase in the mouse brain under conditions simulating the handling of human autopsy material. J Neurochem 31: 381–383
Wong DF, Wagner Jr HN, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA, Toung JKT, 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
Zemlan FP, Hitzemann RJ, Hirschowitz J, Garver DL (1985) Down-regulation of central dopamine receptors in schizophrenia. Am J Psychiatry 142: 1334–1337
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hetey, L., Schwitzkowsky, R., Ott, T. et al. Diminished synaptosomal dopamine (DA) release and DA autoreceptor supersensitivity in schizophrenia. J. Neural Transmission 83, 25–35 (1991). https://doi.org/10.1007/BF01244449
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01244449