Summary
We examined the effects of long-term treatment with haloperidol and clozapine on dopamine D4 receptors in rat frontal cortex. Dopamine D4 receptor binding sites were indirectly determined from the displacement experiments of [3H]clozapine binding using nemonapride. Three-weeks administration of haloperidol (0.5mg/kg) or clozapine (10mg/kg) did not significantly affect the D4 receptors in the frontal cortex. The density of D2 receptors, determined by [3H]spiperone binding to striatum, was increased by long-term treatment with haloperidol, but it was not significantly changed by that with clozapine.
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References
Kusumi I, Matsubara S, Takahashi Y, Ishikane T, Koyama T (1995) Characterization of [3H]clozapine binding sites in rat brain. J Neural Transm (in press)
Lee T, Tang SW (1984) Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain. Psychiat Res 12: 277–285
Meltzer HY, Matsubara S, Lee J-C (1989) Classification of typical and atypical antipsychotic drugs on basis of dopamine D-1, D-2 and serotonin 2 pKi values. J Pharmacol Exp Ther 251: 238–246
Muller P, Seeman P (1977) Brain neurotransmitter receptors after long-term haloperidol: dopamine, acethylcholine, serotonin, alpha-adrenergic and naloxone receptors. Life Sci 21: 1751–1758
Owen F, Cross AJ, Waddington JL, Poulter M, Gamble SJ, Crow TJ (1980) Dopaminemediated behaviour and3H-spiperone binding to striatal membranes in rats after nine months haloperidol administration. Life Sci 26: 55–59
Rupniak NMJ, Hall MD, Mann S, Fleminger S, Kilpatrick G, Jenner P, Marsden CD (1985) Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D-2 receptor function in the rat. Biochem Pharmacol 34: 2755–2763
Schoots O, Seeman P, Guan H-G, Paterson A, Van Tol HHM (1995) Long-term haloperidol elevates dopamine D4 receptors by two-fold in rats. Eur J Pharmacol (in press)
Seeman P (1992) Dopamine receptor sequences: therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. Neuropsychopharmacology 7: 261–284
Seeman P, Guan H-C, Van Tol HHM (1993) Dopamine D4 receptors elevated in schizophrenia. Nature 365: 441–445
Van Tol HHM, Bunzow JR, Guan H-C, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of the gene for a human D4 receptor with high affinity for the antipsychotic clozapine. Nature 350: 610–614
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Kusumi, I., Ishikane, T., Matsubara, S. et al. Long-term treatment with haloperidol or clozapine does not affect dopamine D4 receptors in rat frontal cortex. J. Neural Transmission 101, 231–235 (1995). https://doi.org/10.1007/BF01271560
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DOI: https://doi.org/10.1007/BF01271560