Nociceptin/orphanin FQ receptors modulate glutamate extracellular levels in the substantia nigra pars reticulata. A microdialysis study in the awake freely moving rat
Section snippets
Experimental procedures
Male Sprague–Dawley rats (300–350 g weight; Stefano Morini, Reggio Emilia, Italy) were kept under regular lighting conditions (12 h light/dark cycle) and given food and water ad libitum. Experiments were carried out in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC) and adequate measures were taken to minimize animal pain or discomfort. The experimental protocols performed in the present study were also approved by the Italian Ministero della Sanità
Results
Basal GLU extracellular levels in the SNr were stable over the time course of the experiment (Fig. 1). Spontaneous GLU output was unaffected by local perfusion with submicromolar (0.1 μM) N/OFQ concentrations but was increased by perfusion with N/OFQ 1 and 10 μM (H=19.77, n=48, P=0.0002; Fig. 1). Basal GLU extracellular levels rose slowly during perfusion with N/OFQ 1 μM (peak effect of 148±9%, 30 min after onset of perfusion) while responding promptly to N/OFQ 10 μM (150±14%, 10 min after
Discussion
A major finding of the present microdialysis study was that perfusion with N/OFQ in the SNr evoked an increase of local GLU extracellular levels which was insensitive to naloxone but prevented by the novel N/OFQ receptor antagonist [Nphe1]N/OFQ(1-13)NH2. The stimulation brought about by N/OFQ was also prevented by the D2 receptor antagonist raclopride and partially antagonized by the GABAA receptor antagonist bicuculline.
The pharmacological approach to the N/OFQ–N/OFQ receptor system has been
Conclusion
The microdialysis technique in awake freely moving rats has allowed the demonstration of a phasic facilitatory regulation of nigral GLU outflow mediated by local perfusion with N/OFQ in the SNr. Naloxone-insensitive and [Nphe1]-sensitive N/OFQ receptors, possibly located on dopaminergic, and perhaps GABAergic, neuronal structures, may be involved. The possibility that the inhibitory effect of [Nphe1] on spontaneous GLU outflow reflects the existence of a N/OFQergic facilitatory tone requires
Acknowledgments
This work has been supported by grants from the Consiglio Nazionale delle Ricerche (No. 9704432CT04) and from the Italian Ministry of the University (co-fin 99).
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