Neuropsychiatric disorders, including schizophrenia and drug addiction, are complex conditions that arise from a combination of genetic, environmental, and neurobiological factors. These disorders significantly impact cognitive function, behavior, and overall quality of life.
Schizophrenia is a severe psychiatric illness characterized by hallucinations, delusions, and cognitive impairment. Despite available antipsychotic medications, many patients experience only partial symptom relief, particularly for cognitive and negative symptoms, with substantial side effects limiting long-term use.
Similarly, drug addiction is a chronic relapsing disorder driven by neurochemical imbalances affecting reward pathways in the brain. Current treatments, such as behavioral therapy and pharmacological interventions, often have limited efficacy and high relapse rates.
The lack of suitable treatments in both conditions highlights the need for novel therapeutic strategies that address underlying neurobiological dysfunctions more effectively, offering better symptom management and improved patient outcomes.
Serotonin (5-HT) receptors and orphan GPCRs play critical roles in the pathophysiology of schizophrenia and drug addiction, making them promising therapeutic targets.
- Serotonin Receptors (5-HTRs): Several serotonin receptor subtypes, particularly 5-HT₂A and 5-HT₁A, are implicated in schizophrenia. Additionally, 5-HT₂C agonists are arising as potential treatment for substance use diseases (reviewed Ubhayarathna et al 2024).
- Orphan GPCRs: These underexplored receptors, with unknown endogenous ligands, are emerging as potential modulators of neuropsychiatric disorders. Some orphan GPCRs influence neurotransmitter release, synaptic plasticity, and neuroinflammation, processes relevant to schizophrenia and addiction (reviewed Yu et al 2023).
Our work to better characterise the roles of these GPCRs, allows us to better develop more targeted and effective therapeutics for these challenging disorders.
