title: Definition of the in-vivo accumulation of [3H]spiperone in brain using haloperidol and sulpiride to determine functional dopamine receptor occupation.
abstract: The in-vivo administration of [3H]spiperone caused an accumulation of radioactivity in the substantia nigra, tuberculum olfactorium, nucleus accumbens, striatum and frontal cortex when compared with cerebellar levels. Haloperidol (0.01-1.0 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone in the substantia nigra, tuberculum olfactorium, striatum and nucleus accumbens. Sulpiride (10-160 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone only in the substantia nigra. The effects of sulpiride on other areas were not consistent; there was a suggestion of a reduction in the accumulation of [3H]spiperone in tuberculum olfactorium and striatum, but not in nucleus accumbens. Neither haloperidol (0.01-1.0 mg kg-1 i.p.) nor sulpiride (10-160 mg kg-1 i.p.) caused displacement of [3H]spiperone from the frontal cortex. Both haloperidol (0.01-0.5 mg kg-1) and sulpiride (10-80 mg kg-1) increased striatal and mesolimbic HVA concentrations. Haloperidol potently blocked apomorphine-induced stereotypy but sulpiride was only effective at the highest dose employed. The functional effect produced by haloperidol correlated with its ability to define [3H]spiperone binding in-vivo to dopamine receptors in the substantia nigra, striatum and tuberculum olfactorium. In contrast, there was no correlation between functional effect of sulpiride and its ability to define [3H]spiperone binding in-vivo.
authors.affiliation: MRC Movement Disorders Research Group, University Department of Neurology, Denmark Hill, London, UK.
authors.forename: J K
authors.initials: JK
authors.lastname: Chivers
authors.forename: C
authors.initials: C
authors.lastname: Reavill
authors.forename: P
authors.initials: P
authors.lastname: Jenner
authors.forename: C D
authors.initials: CD
authors.lastname: Marsden
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006220:Haloperidol; D006719:Homovanillic Acid / Q000378:metabolism; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects; D013469:Sulpiride
chemical_list: D011954:Receptors, Dopamine; D013134:Spiperone; D013469:Sulpiride; D006220:Haloperidol; D001058:Apomorphine; D006719:Homovanillic Acid