p(HGNC:DRD1)

Entity

Name

DRD1

Namespace

hgnc

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

M4 mAChR is also involved in the pathology of Parkinson’s disease, which is associated with the loss of dopaminergic neurons projecting to the striatum and an imbalance between cholinergic and dopaminergic systems. In the corpus striatum, M4 mAChR is closely co-localized with dopamine receptors on striatal-projecting neurons and the striatal M4 mAChR inhibits dopamine D1 receptor function. Mice lacking M4 mAChR show increased locomotor activity and enhanced dopamine D1 receptor-mediated effects[55]. Consequently, selective M4 mAChR antagonists, such as benzoxazines, have been developed for the treatment of Parkinson’s disease PubMed:24590577

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

In line with this, experimental models of DISC1 deficiency treated with METH show a significant potentiation of DA release, along with increased expression of D1R in the ventral striatum when compared with controls PubMed:30061532

Increased activity of D1R is considered as a major determinant of neuropsychiatric alterations occurring in both METH models/abusers and in schizophrenia PubMed:30061532

Increased activity of D1R is considered as a major determinant of neuropsychiatric alterations occurring in both METH models/abusers and in schizophrenia PubMed:30061532

This is key, because abnormal stimulation of D1R and subsequent signaling cascades were recently shown to produce an over-activation of mTOR and inhibition of the autophagy machinery PubMed:30061532

Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532

This is key, because abnormal stimulation of D1R and subsequent signaling cascades were recently shown to produce an over-activation of mTOR and inhibition of the autophagy machinery PubMed:30061532

In line with this, experimental models of DISC1 deficiency treated with METH show a significant potentiation of DA release, along with increased expression of D1R in the ventral striatum when compared with controls PubMed:30061532

Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532

Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532

Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532

In detail, the activation of CDK5 by D1R occurs via proteolysis of p35, the binding partner of CDK5 PubMed:30061532