Regulation of striatal nitric oxide synthesis by local dopamine and glutamate interactions
Article first published online: 3 OCT 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 111, Issue 6, pages 1457–1465, December 2009
How to Cite
Park, D. J. and West, A. R. (2009), Regulation of striatal nitric oxide synthesis by local dopamine and glutamate interactions. Journal of Neurochemistry, 111: 1457–1465. doi: 10.1111/j.1471-4159.2009.06416.x
- Issue published online: 20 NOV 2009
- Article first published online: 3 OCT 2009
- Received July 24, 2009; revised manuscript received September 21, 2009; accepted September 23, 2009.
- D1/5 receptor;
- dorsal striatum;
- neuronal nitric oxide synthase;
- nitric oxide;
- NMDA receptor
Nitric oxide (NO) is a key neuromodulator of corticostriatal synaptic transmission. We have shown previously that dopamine (DA) D1/5 receptor stimulation facilitates neuronal NO synthase (nNOS) activity in the intact striatum. To study the impact of local manipulations of D1/5 and glutamatergic NMDA receptors on striatal nNOS activity, we combined the techniques of in vivo amperometry and reverse microdialysis. Striatal NO efflux was monitored proximal to the microdialysis probe in urethane-anesthetized rats during local infusion of vehicle or drug. NO efflux elicited by systemic administration of SKF-81297 was blocked following intrastriatal infusion of: (i) the D1/5 receptor antagonist SCH-23390, (ii) the nNOS inhibitor 7-nitroindazole, (iii) the non-specific ionotropic glutamate receptor antagonist kynurenic acid, and (iv) the selective NMDA receptor antagonist 3-phosphonopropyl-piperazine-2-carboxylic acid. Glycine co-perfusion did not affect SKF-81297-induced NO efflux. Furthermore, intrastriatal infusion of SKF-81297 potentiated NO efflux evoked during electrical stimulation of the motor cortex. The facilitatory effects of cortical stimulation and SKF-81297 were both blocked by intrastriatal infusion of SCH-23390, indicating that striatal D1/5 receptor activation is necessary for the activation of nNOS by corticostriatal afferents. These studies demonstrate for the first time that reciprocal DA-glutamate interactions play a critical role in stimulating striatal nNOS activity.