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Updated: Jul 17, 2026
09:54
Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
Published on: August 10, 2012
Dopamine D2 receptor-dependent modulation of striatal NO synthase activity
Stephen Sammut1, Kristina E Bray, Anthony R West
1Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, USA.
Psychopharmacology
|January 9, 2007
Summary
Dopamine D2 receptor activation down-regulates nitric oxide (NO) synthesis in the striatum, opposing dopamine D1 receptor effects. This finding is crucial for understanding antipsychotic drug mechanisms and potential new treatments.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Striatal nitric oxide (NO) signaling is modulated by dopamine (DA) transmission.
- Antipsychotic drugs can increase neuronal NO synthase (NOS) expression, suggesting a link between NO and antipsychotic action.
Purpose of the Study:
- To investigate how dopamine D2 receptor activation influences striatal NO production in vivo.
- To elucidate the role of dopaminergic regulation of NO signaling in the context of antipsychotic drug mechanisms.
Main Methods:
- Assessed striatal NO efflux using an NO-selective amperometric microsensor in anesthetized rats.
- Stimulated NO release via electrical stimulation of the substantia nigra or administration of dopamine D1 receptor agonist SKF 81297.
Main Results:
- Dopamine D2 receptor agonist quinpirole attenuated NO efflux evoked by substantia nigra stimulation.
- Dopamine D2 receptor antagonist eticlopride enhanced evoked NO efflux.
- Quinpirole reduced SKF 81297-induced NO efflux, which was reversed by eticlopride; methylene blue inhibited NO efflux.
Conclusions:
- Dopamine D2 receptor activation inhibits NO synthesis in the striatum through a D2 receptor-dependent pathway.
- Dopamine D2 receptor activity counteracts dopamine D1 receptor-mediated NO synthesis postsynaptically.
- Further research into NO-dopamine interactions may yield novel therapeutic strategies for brain disorders.
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