Nociceptin/orphanin FQ receptors modulate glutamate extracellular levels in the substantia nigra pars reticulata. A microdialysis study in the awake freely moving rat.

摘要

Intracerebral microdialysis was employed in awake freely moving rats to investigate the effects of nociceptin/orphanin FQ receptor ligands on glutamate extracellular levels in the substantia nigra pars reticulata. Nociceptin/orphanin FQ, ineffective at 0.1 &mgr;M, induced a prolonged stimulation of nigral glutamate levels at 1 and 10 &mgr;M (mean effect of 137+/-9 and 167+/-13%, respectively, of basal values). These effects were prevented by the novel nociceptin/orphanin FQ receptor antagonist [Nphe(1)]nociceptin/orphanin FQ(1-13)NH(2) (100 and 300 &mgr;M, respectively) but not by the non-selective opioid receptor antagonist naloxone (10 &mgr;M). [Nphe(1)]nociceptin/orphanin FQ(1-13)NH(2) (100 &mgr;M) inhibited by itself glutamate outflow (maximal reduction to 71+/-4%) while naloxone was ineffective. The nociceptin/orphanin FQ receptor ligand [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin/orphanin FQ(1-13)NH(2) also facilitated glutamate outflow at 10 &mgr;M (mean effect of 145+/-10%). Intranigral perfusion with tetrodotoxin (1 &mgr;M) or with the dopamine D(2) receptor antagonist raclopride (1 &mgr;M), failed to affect basal glutamate output and prevented the facilitatory effect of nociceptin/orphanin FQ (10 &mgr;M). However, perfusion with the GABA(A) receptor antagonist bicuculline (10 &mgr;M) increased local glutamate extracellular levels by itself and attenuated the effect of the peptide.Our data suggest that nociceptin/orphanin FQ increases glutamate extracellular levels in the substantia nigra pars reticulata via activation of nociceptin/orphanin FQ receptors located on non-glutamatergic, possibly dopaminergic and GABAergic, neuronal elements.