This intracellular cross-talk results in modified signaling directed by the heterodimer which may underlie the pathogenesis of schizophrenia: e.g., H3-D1 receptor heteromer induces a Gi protein mediated activation of MAPK pathway (Ferrada et al., 2009) whereas H3-D1/D2 heteromers exhibited an antagonistic interaction as H3R agonism negatively modulated D1 or D2 receptor function (Ferrada et al., 2008). This evidence concerns the gene HRH3 and schizophrenia.