Phenylalanine Rich Diet (Vicia faba L.) Enhances the Expression of Dopamine Receptor D3 (DRD3) Gene in Rabbits

Dopamine is a neurotransmitter hormone for pleasure and reward. It is synthesized only in the brain cells of human and animals and responsible for the regulation of behavior, mood, memory, cognitive, flexible movement, the body weight, and other important functions. The Dopamine Receptor D3 (DRD3) is the most important receptor for dopamine. In this investigation, expression of DRD3 gene was studied in rabbits fed on supplemented diet of dry and fresh faba bean (Vicia faba L. Sakha 3). DRD3 gene (≈ 1200 bp) in control and treated rabbits were PCR amplified, sequenced and aligned with reference gene (Acc. No XM_017346708.1). High genetic similarity values were detected among all sequences. DRD3 gene sequences of control, fresh and dry faba bean fed rabbits were deposited in the GenBank with accession numbers MZ714134, MZ714135 and MZ714136 respectively. Direct estimation of blood phenylalanine (Phe) amino acid indicated that feeding rabbits on dry faba bean reflected the highest level of Phe in the rabbit’s blood. Quantitative RT-qPCR analysis showed that DRD3 gene was over expressed after feeding rabbits on dry faba bean form compared with feeding on green form and control. Thus, diet rich with phenylalanine like Sakha3 (dry and fresh forms) enhance gene expression of DRD3 gene. However, diet doesn't affect the DRD3 gene sequence and structure. In a conclusion, our findings indicated a direct effect of faba bean supplemented diet on increasing DRD3 expression levels which improve the life quality for human.

DRD3 gene and striatum in autism spectrum disorder

SummaryA single-nucleotide polymorphism (SNP) of the DRD3 gene (rs167771) was recently associated with autism spectrum disorders (ASD). Different polymorphisms of rs167771 corresponded to varying degrees of stereotyped behaviour. As DRD3 receptors are relatively overexpressed in the striatum, we investigated whether striatal volume was related to these polymorphisms in autism. We assessed volumes of caudate nucleus and putamen in 86 participants with ASD (mean age 15.3 years). MANCOVA showed an association between alleles of the rs167771 SNP and the volume of striatal structures. Furthermore, greater caudate nucleus volume correlated with stereotyped behaviour. These findings support a relationship between DRD3 gene SNPs, striatum and stereotyped behaviour in ASD.

Dopamine D3 receptor gene variation: impact on electroconvulsive therapy response and ventral striatum responsiveness in depression

Dysfunction of dopamine D3 receptors, particularly in the mesocorticolimbic system, has been linked to the pathogenesis of major depression. Preclinical data show enhanced D3 receptor binding in the striatum upon antidepressant medication and electroconvulsive therapy (ECT). Thus, the potential impact of dopamine D3 receptor gene (DRD3) variation on ECT outcome in treatment-resistant major depression was evaluated by applying a combined molecular and imaging genetic approach. Altogether, 10 representative variants covering 95.4% of DRD3 gene variation were investigated for association with response to ECT in a sample of 104 (71 female, 33 male) Caucasian patients with pharmacorefractory major depression. Additionally, ventral striatum responsiveness to happy faces was assessed in two independent samples of depressed patients (total N=54) by means of functional magnetic resonance imaging at 3 T. Significant association of DRD3 rs3732790, rs3773679 and rs9817063 variants with response (uncorrected p=0.02–0.03) and remission (uncorrected p=0.01) after ECT was discerned. Logistic regression analyses revealed association of rs3732790 (uncorrected p=0.009; corrected p=0.045) and rs3773679 (uncorrected p=0.009; corrected p=0.045) with remission when applying a recessive model of inheritance. The rs3732790T allele conferring a more favourable treatment response was furthermore found to be associated with stronger striatal responsiveness to happy facial expressions (sample 1: cluster-corrected p=0.002; sample 2: p=0.023). In summary, the present study suggests some impact of DRD3 gene variation on ECT response, potentially mediated by alteration of striatal engagement during the processing of emotionally rewarding stimuli.