Dopamine Receptors: Is It Possible to Become a Therapeutic Target for Depression?

Abstract

Dopamine and its receptors are currently recognized targets for the treatment of several neuropsychiatric disorders, including Parkinson’s disease, schizophrenia, some drug use addictions, as well as depression. Dopamine receptors are widely distributed in various regions of the brain, but their role and exact contribution to neuropsychiatric diseases has not yet been thoroughly studied. Based on the types of dopamine receptors and their distribution in different brain regions, this paper reviews the current research status of the molecular, cellular and circuit mechanisms of dopamine and its receptors involved in depression. Multiple lines of investigation of these mechanisms provide a new future direction for understanding the etiology and treatment of depression and potential new targets for antidepressant treatments.

Dopaminergic Modulation and Computational ADMET Insights for the Antidepressant-like Effect of N-(3-(Phenylselanyl)prop-2-yn-1-yl)benzamide

“…Demotivational symptoms in MDD, such as depressed mood, decreased energy, and anhedonia, appear to be related to a dysfunction of the dopaminergic system. 18 A clinical study linked the symptoms of anhedonia in patients with depression with decreased DA release signaling in brain regions, such as the putamen, caudate, nucleus accumbens, and pallidum. 26 Patients with anhedonia may present a more severe clinical picture, 16 which is related to resistance to treatment with selective serotonin reuptake inhibitors (SSRIs).…”

“…17 Dopamine (DA), a monoaminergic neurotransmitter, modulates the reward system. 18 Decreased DA signaling in the mesocorticolimbic pathway of the brain appears to result in demotivational depressive symptoms such as depressed mood, decreased energy, and anhedonia. 19,20 Increasing dopaminergic neurotransmission has been shown to alleviate depressive symptoms, 21 suggesting that compounds with the ability to modulate the dopaminergic system may hold promise as a more effective treatment for MDD.…”

Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice

“…In this study, we selected another arylpiperazine derivative of salicylamide, JJGW07, due to its high affinity for serotonin 5-HT 1A , moderate affinity for 5-HT 7 and D 2 , and weak affinity for 5-HT 2A receptors [ 5 ]. As these receptors are widely distributed in various brain regions, they are associated with diverse CNS disorders, including depression, anxiety, schizophrenia, and memory disturbances [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Scientists have discovered that both agonists and antagonists of the 5-HT 1A receptor may possess antidepressant and/or anxiolytic activity [ 9 ], whereas agonists or partial agonists may demonstrate antipsychotic or procognitive potential [ 14 , 15 , 16 , 17 ].…”

“…Further, serotonin 5-HT 7 receptor antagonists may possess antidepressant and antipsychotic activity, whereas both agonists and antagonists can demonstrate anxiolytic effects and memory-enhancing properties [ 9 , 14 , 19 , 20 , 21 , 22 ]. Finally, dopamine D 2 receptor antagonists or partial agonists may reduce the symptoms of schizophrenia, whereas agonists can ameliorate depression-like conditions [ 8 , 23 , 24 , 25 ]. Taking the above into account, as well as considering the receptor profile of JJGW07 and our previous studies on the arylpiperazine derivative of salicylamide, we aimed to assess the antidepressant-like, anxiolytic-like, and antipsychotic-like effects of JJGW07 in mice.…”

Stapling Amantadine to Melanostatin Neuropeptide: Discovery of Potent Positive Allosteric Modulators of the D2 Receptors

“…Because of its pharmacological repertoire, MIF-1 has a therapeutical potential in neurological disorders associated with the D 2 R, such as depression, tardive dyskinesia, restless legs syndrome, and Parkinson’s disease (PD) . In fact, MIF-1 is one of the few peptides with a partially saturable influx system at the blood–brain barrier (BBB) allowing it to accumulate in the central nervous system (CNS) .…”