Back to Search
Start Over
Dopaminergic modulation of nitric oxide synthase activity in subregions of the rat nucleus accumbens
- Source :
- Synapse. 66:220-231
- Publication Year :
- 2011
- Publisher :
- Wiley, 2011.
-
Abstract
- Nitric oxide (NO) is a gaseous neurotransmitter synthesized in the nucleus accumbens (NAc) by aspiny interneurons containing neuronal NO synthase (nNOS). nNOS activity is readily assayed using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining and is believed to be regulated by activation of dopamine (DA) D1- and D2-like receptors. However, the role of DA transmission in the regulation of nNOS activity in identified subregions of the NAc remains unexplored. In this study, the impact of pharmacological manipulations of D1, D2, and NMDA receptors on nNOS activity was determined using optical density measures of NADPH-d staining preformed in multiple subdivisions (core, medial shell, intermediate shell, and lateral shell) of the NAc. Awake behaving rats received systemic administration of vehicle and/or the following drugs ~25 min prior to tissue harvesting: the nNOS inhibitor N(G) -propyl-L-arginine (NPA), the D1 receptor agonist SKF 81297, the D1 receptor antagonist SCH 23390, the D2 receptor agonist quinpirole (QNP), the D2 receptor antagonist eticlopride (ETI), or the NMDA receptor antagonist 3-((±)2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). In vehicle-treated animals, a distinct medial-lateral histochemical gradient of NADPH-d staining was observed, which was characterized by moderate staining in the core and medial shell and more robust staining in the intermediate and lateral shell. Administration of NPA, SCH 23390, QNP, and CPP attenuated staining preferentially in the intermediate and lateral shell. SKF 81297 and ETI administration consistently increased staining in the medial shell in a manner, which was attenuated following pretreatment with SCH 23390, QNP, NPA, and CPP. These observations demonstrate that nNOS activity measured in distinct subregions of the NAc is differentially modulated by DA D1 and D2 receptor activation. Moreover, these findings demonstrate for the first time that DA D1 and D2 receptor activation regulates the facilitatory influence of glutamatergic transmission on nNOS activity in the NAc medial shell via facilitation (D1) or suppression (D2) of NMDA receptor function.
- Subjects :
- Male
Agonist
Quinpirole
medicine.drug_class
Dopamine
Nucleus accumbens
Pharmacology
Arginine
Receptors, N-Methyl-D-Aspartate
Nucleus Accumbens
Piperazines
Rats, Sprague-Dawley
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Eticlopride
Dopamine receptor D1
Dopamine receptor D2
Salicylamides
medicine
Animals
SCH-23390
Receptors, Dopamine D2
Chemistry
Dopaminergic Neurons
Receptors, Dopamine D1
Benzazepines
Rats
Dopamine D2 Receptor Antagonists
nervous system
Biochemistry
Dopamine Agonists
Dopamine Antagonists
NMDA receptor
Nitric Oxide Synthase
medicine.drug
Subjects
Details
- ISSN :
- 08874476
- Volume :
- 66
- Database :
- OpenAIRE
- Journal :
- Synapse
- Accession number :
- edsair.doi.dedup.....a7532acf5033ea7bc4e592a6fc55bf5b