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Several lines of evidence indicate the key role of G protein\u2010coupled receptors (<jats:styled-content style=\"fixed-case\">GPCR<\/jats:styled-content>s) heteromers in pathophysiology of schizophrenia and highlight these complexes as novel drug targets. Because heterodimers can form only on those cells co\u2010expressing constituent receptors, they present a target of high pharmacological specificity in the context of biochemical effects induced by antipsychotic drugs. In studies conducted in the <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content> 293 cell line, we demonstrated that 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1<\/jats:sub><jats:styled-content style=\"fixed-case\"><jats:sub>A<\/jats:sub>R<\/jats:styled-content> and D<jats:sub>2<\/jats:sub>R are able to form constitutive heterodimers, and antipsychotic drugs (clozapine, olanzapine, aripiprazole, and lurasidone) enhanced this process, with clozapine being most effective. Various functional tests (<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content><jats:sub>1<\/jats:sub> as well as <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> activation) indicated that the drugs had different effects on signal transduction by the heteromer. Interestingly, co\u2010incubation of heterodimer\u2010expressing <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content> 293 cells with clozapine and the 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1<\/jats:sub><jats:styled-content style=\"fixed-case\"><jats:sub>A<\/jats:sub>R<\/jats:styled-content> agonist 8\u2010<jats:styled-content style=\"fixed-case\">OH DPAT<\/jats:styled-content> potentiated post\u2010synaptic effects, especially with respect to <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> activation. Our results indicate that the D<jats:sub>2<\/jats:sub>\u20105\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub> complex possesses biochemical, pharmacological, and functional properties distinct from those of mono\u2010 and homomers. This result has implications for the development of improved pharmacotherapy for schizophrenia or other disorders (activating the heteromer might be cognitive enhancing, since it is expressed in frontal cortex) through the specific targeting of heterodimers.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13582-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nWe reported the constitutive formation of D<jats:sub>2<\/jats:sub>\u20105\u2010HT<jats:sub>1A<\/jats:sub> heteromers, which possess biochemical, pharmacological, and functional properties distinct from those of mono\u2010 and homomers, as revealed by antipsychotics action. We also showed that these two receptors are co\u2010expressed in mouse cortical neurons; therefore their potential to heterodimerize may comprise an essential target for the development of novel strategies for schizophrenia treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13582","type":"journal-article","created":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T03:16:38Z","timestamp":1455506198000},"page":"549-560","source":"Crossref","is-referenced-by-count":59,"title":["Dopamine D<sub>2<\/sub> and serotonin 5\u2010<scp>HT<\/scp><sub>1A<\/sub> receptor interaction in the context of the effects of antipsychotics \u2013 <i>in\u00a0vitro<\/i> studies"],"prefix":"10.1111","volume":"137","author":[{"given":"Sylwia","family":"\u0141ukasiewicz","sequence":"first","affiliation":[{"name":"Department of Physical Biochemistry Faculty of Biochemistry Biophysics and Biotechnology Jagiellonian University Krakow 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