title: Adenosine and dopamine receptor antagonist binding in the rat ventral and dorsal striatum: lack of changes after a neonatal bilateral lesion of the ventral hippocampus.
abstract: There is experimental evidence from radioligand binding experiments for the existence of strong antagonistic interactions between different subtypes of adenosine and dopamine receptors in the striatum, mainly between adenosine A1 and dopamine D1 and between adenosine A2A and dopamine D2 receptors. These interactions seem to be more powerful in the ventral compared to the dorsal striatum, which might have some implications for the treatment of schizophrenia. The binding characteristics of different dopamine and adenosine receptor subtypes were analysed in the different striatal compartments (dorsolateral striatum and shell and core of the nucleus accumbens), by performing saturation experiments with the dopamine D1 receptor antagonist [125I]SCH-23982, the dopamine D2-3 receptor antagonist [3H]raclopride, the adenosine A1 receptor antagonist [3H]DPCPX and the adenosine A2A receptor antagonist [3H]SCH 58261. The experiments were also performed in rats with a neonatal bilateral lesion of the ventral hippocampus (VH), a possible animal model of schizophrenia. Both dopamine D2-3 and adenosine A2A receptors follow a similar pattern, with a lower density of receptors (40%) in the shell of the nucleus accumbens compared with the dorsolateral caudate-putamen. A lower density of adenosine A1 receptors (20%) was also found in the shell of the nucleus accumbens compared with the caudate-putamen. On the other hand, dopamine D1 receptors showed a similar density in the different striatal compartments. Therefore, differences in receptor densities cannot explain the stronger interactions between adenosine and dopamine receptors found in the ventral, compared to the dorsal striatum. No statistical differences in the binding characteristics of any of the different adenosine and dopamine receptor antagonists used were found between sham-operated and VH-lesioned rats.
authors.affiliation: Clinical Brain Disorders Branch, National Institute of Mental Health, Washington, DC 20032, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Lillrank
authors.forename: B K
authors.initials: BK
authors.lastname: Lipska
authors.forename: D R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: B B
authors.initials: BB
authors.lastname: Fredholm
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
authors.forename: S
authors.initials: S
authors.lastname: Ferré
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000494:pharmacology; D001552:Benzazepines / Q000031:analogs & derivatives / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011247:Pregnancy; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000378:metabolism; D020891:Raclopride; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012457:Salicylamides / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D014150:Antipsychotic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D012457:Salicylamides; D014230:Triazoles; D014970:Xanthines; D020891:Raclopride; C051360:1,3-dipropyl-8-cyclopentylxanthine