Delta opioid receptors in brain function and diseases.

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• The delta opioid receptor (DOR) is widely expressed in the brain and distinct from mu and kappa opioid receptors.
• Recent evidence highlights DOR as a significant target for treating various brain disorders.
• Knowledge of DOR function has advanced through in vivo studies using pharmacological and genetic tools.

Purpose of the Study:

• To review the role of delta opioid receptor activity in psychiatric and neurological disorders, beyond its established function in chronic pain.
• To explore the potential therapeutic applications of DOR agonists in mood disorders, emotional responses, and drug abuse.
• To investigate the drug-dependent effects of DOR agonists, including epileptogenic and locomotor-stimulating effects, and the potential for biased agonism.

Main Methods:

• Review of in vivo studies utilizing pharmacological tools and genetic approaches.
• Analysis of existing literature on DOR function in the context of neurological and psychiatric conditions.
• Exploration of emerging research areas such as neuroprotection and cellular/circuit-level DOR function.

Main Results:

• DOR agonists demonstrate beneficial effects in managing emotional responses and mood disorders.
• DOR activation influences drug reward, inhibitory control, and learning processes, with ongoing questions regarding its efficacy in treating drug abuse.
• Epileptogenic and locomotor-stimulating effects of DOR agonists are drug-dependent, suggesting potential for biased agonism to improve therapeutic ratios.

Conclusions:

• DOR is a promising target for neurological and psychiatric disorders, with established benefits in mood regulation.
• Further investigation into biased agonism at DOR is warranted to optimize therapeutic benefits and minimize side effects.
• Future research should focus on cellular and circuit-level DOR functions and its neuroprotective potential.