Paroxetine and Low-dose Risperidone Induce Serotonin 5-HT and Dopamine D2 Receptor Heteromerization in the Mouse Prefrontal Cortex.

Recently, it has been shown that serotonin 5-HT receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT-D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT-D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10 mg/kg) or risperidone (0.

Antidepressants promote formation of heterocomplexes of dopamine D2 and somatostatin subtype 5 receptors in the mouse striatum.

The interaction between the dopaminergic and somatostatinergic systems is considered to play a potential role in mood regulation. Chronic administration of antidepressants influences release of both neurotransmitters. The molecular basis of the functional cooperation may stem from the physical interaction of somatostatin receptor subtypes and dopamine D2 receptors since they colocalize in striatal interneurons and were shown to undergo ligand-dependent heterodimerization in heterologous expression systems.

Basal prolactin levels in rat plasma correlates with response to antidepressant treatment in animal model of depression.

Prolactin (PRL) has been shown to be altered by psychotropic drugs, including antidepressant drugs (ADs). Many studies have focused on the response to antidepressant treatment (especially related to the serotonergic system) using the fenfluramine test (PRF), however some data suggest lack of correlation between PRF and prediction of clinical response to ADs. In our study we have investigated the hypothesis that basal plasma level of prolactin is a better predictor of antidepressant treatment.

Genetic variants of dopamine D2 receptor impact heterodimerization with dopamine D1 receptor.

Background: The human dopamine D2 receptor gene has three polymorphic variants that alter its amino acid sequence: alanine substitution by valine in position 96 (V96A), proline substitution by serine in position 310 (P310S) and serine substitution by cysteine in position 311 (S311C). Their functional role has never been the object of extensive studies, even though there is some evidence that their occurrence correlates with schizophrenia.

Methods: The HEK293 cell line was transfected with dopamine D1 and D2 receptors (or genetic variants of the D2 receptor), coupled to fluorescent proteins which allowed us to measure the extent of dimerization of these receptors, using a highly advanced biophysical approach (FLIM-FRET).

Dopamine D2 and serotonin 5-HT1A receptor interaction in the context of the effects of antipsychotics - in vitro studies.

The serotonin 5-HT1A receptor (5-HT1 A R) and dopamine D2 receptor (D2 R) have been implicated as important sites of action in antipsychotics. Several lines of evidence indicate the key role of G protein-coupled receptors (GPCRs) heteromers in pathophysiology of schizophrenia and highlight these complexes as novel drug targets. Because heterodimers can form only on those cells co-expressing constituent receptors, they present a target of high pharmacological specificity in the context of biochemical effects induced by antipsychotic drugs.