title: Alterations in ventral and dorsal striatal allosteric A2AR-D2R receptor-receptor interactions after amphetamine challenge: Relevance for schizophrenia.
abstract: Striatal dopamine D2R homodimerization is increased in the dorsal striatum after acute amphetamine challenge and in the amphetamine-induced sensitized state, a well-known animal model of schizophrenia. Therefore, it was tested if the increase in D2R homoreceptor complexes found after acute amphetamine challenge in the saline or the amphetamine sensitized state leads to changes in the antagonistic adenosine A2AR-D2R interactions in the striatum. [3H]-raclopride binding was performed in membrane preparations from the ventral and dorsal striatum involving competition with the D2R like agonist quinpirole. In the ventral striatum CGS 21680 produced a significant increase of the KiHvalues (p<0.05) in the amphetamine sensitized group when expressed in percent versus the corresponding values in saline sensitized rats after amphetamine challenge. However, in the dorsal striatum a significant change did not develop in the KiHvalues when expressed in percent of the corresponding values in saline sensitized rats after amphetamine challenge. In fact, the non-significant change was in the opposite direction towards a reduction of the KiHvalues. Taken together, a reduced affinity of the high affinity D2 agonist binding site (KiHvalue) developed in the ventral but not in the dorsal striatum as a result of increased antagonistic allosteric A2AR-D2R interactions in the amphetamine-induced sensitized state versus the saline sensitized state after an acute amphetamine challenge. The selective reappearance of antagonistic A2AR-D2R receptor-receptor interactions in the ventral striatum after amphetamine challenge in the amphetamine sensitized rat may give one possible mechanism for the atypical antipsychotic-like actions of A2AR receptor agonists.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden; Institute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. Electronic address: juliaofli@gmail.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Pintsuk
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden; Department of Earth, Life and Environmental Sciences, Section of Physiology, Campus Scientifico Enrico Mattei, via Ca' le Suore 2, I-61029 Urbino, Italy. Electronic address: dasiel.borroto.escuela@ki.se.
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.affiliation: Campbell Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario M5T 1R8, Canada. Electronic address: Terence.Lai@camh.ca.
authors.forename: Terence K Y
authors.initials: TK
authors.lastname: Lai
authors.affiliation: Campbell Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario M5T 1R8, Canada. Electronic address: Fang.Liu@camh.ca.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. Electronic address: kjell.fuxe@ki.se.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
keywords: Adenosine A2A receptor; Allosteric receptor-receptor interaction; Amphetamine; Dopamine D2 receptor; Heteroreceptor complexes; Schizophrenia