Drd3-KO Mouse

Drd3, short for dopamine receptor D3, is a key component in the dopamine-mediated signaling pathways. Dopamine receptors are integral to the regulation of various physiological and neurological functions, with Drd3 playing a role in processes like autophagy regulation, and is associated with the basal ganglia-frontal lobe circuitry [3]. It is highly expressed in the basal ganglia, particularly the caudate nucleus [1].

The SNP rs167771 of Drd3 has been associated with autism spectrum disorder (ASD), and its polymorphisms are related to repetitive and stereotyped behavior in ASD patients. The rs167771 SNP was also found to be related to risperidone-induced extra-pyramidal side effects in autistic patients [1]. In schizophrenia, the Ser9Gly polymorphism of Drd3 was significantly associated with treatment response to antipsychotic drugs in Caucasians but not in Asians [2]. Early life stress-induced downregulation of Drd3 signaling in the lateral septum causes social abnormalities in adulthood, and its activation can rescue these impairments [4]. Also, certain Drd3 genotypes are associated with high treatment resistance to second-generation antipsychotics in patients with treatment-resistant mental disorders [5]. In Parkinson's disease, the rs6280 CC genotype of Drd3 predisposes to executive and visuoconstructional deficits, while the TC genotype protects from anxiety [6].

In conclusion, Drd3 is crucial in the regulation of neurological functions and is associated with multiple neuropsychiatric disorders including autism, schizophrenia, and Parkinson's disease. Findings from genetic studies, especially those focusing on SNPs, have revealed its role in disease-related behaviors and treatment responses, contributing to a better understanding of the underlying mechanisms and potentially guiding future therapeutic strategies.

References:

1. Staal, Wouter G. 2014. Autism, DRD3 and repetitive and stereotyped behavior, an overview of the current knowledge. In European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 25, 1421-6. doi:10.1016/j.euroneuro.2014.08.011. https://pubmed.ncbi.nlm.nih.gov/25224105/

2. Liu, Chuanyong, Xu, Xiaohong, Liu, Xiaoyan, Li, Yaoyao, Yan, Pan. 2022. DRD3 Ser9Gly polymorphism and treatment response to antipsychotics in schizophrenia: A meta-analysis. In Neuroscience letters, 786, 136788. doi:10.1016/j.neulet.2022.136788. https://pubmed.ncbi.nlm.nih.gov/35835396/

3. Barroso-Chinea, Pedro, Luis-Ravelo, Diego, Fumagallo-Reading, Felipe, Millan, Mark J, Gonzalez-Hernandez, Tomas. 2019. DRD3 (dopamine receptor D3) but not DRD2 activates autophagy through MTORC1 inhibition preserving protein synthesis. In Autophagy, 16, 1279-1295. doi:10.1080/15548627.2019.1668606. https://pubmed.ncbi.nlm.nih.gov/31538542/

4. Shin, Sora, Pribiag, Horia, Lilascharoen, Varoth, Wang, Xiao-Yun, Lim, Byung Kook. 2017. Drd3 Signaling in the Lateral Septum Mediates Early Life Stress-Induced Social Dysfunction. In Neuron, 97, 195-208.e6. doi:10.1016/j.neuron.2017.11.040. https://pubmed.ncbi.nlm.nih.gov/29276054/

5. Del Casale, Antonio, Simmaco, Maurizio, Modesti, Martina Nicole, Girardi, Paolo, Pompili, Maurizio. 2023. DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs. In Biomedicines, 11, . doi:10.3390/biomedicines11072088. https://pubmed.ncbi.nlm.nih.gov/37509727/

6. Gonçalves, Alexandra, Mendes, Alexandre, Damásio, Joana, Leal, Bárbara, Cavaco, Sara. . DRD3 Predicts Cognitive Impairment and Anxiety in Parkinson's Disease: Susceptibility and Protective Effects. In Journal of Parkinson's disease, 14, 313-324. doi:10.3233/JPD-230292. https://pubmed.ncbi.nlm.nih.gov/38363619/