Striatal dopamine–NMDA receptor interactions in the modulation of glutamate release in the substantia nigra pars reticulata in vivo: opposite role for D₁ and D₂ receptors

Abstract

Dual probe microdialysis was employed in conscious rats to investigate whether endogenous dopamine is involved in the stimulation of glutamate release in the substantia nigra pars reticulata following striatal NMDA receptor activation. Intrastriatal perfusion with NMDA (1 and 10 lM) facilitated nigral glutamate release (dizocilpine-and tetrodotoxin-sensitive). The D 2 dopamine receptor antagonist raclopride increased spontaneous nigral glutamate release and caused a leftward shift in the NMDA sensitivity, lowering NMDA effective concentrations to submicromolar levels. Conversely, the D 1 antagonist SCH23390 prevented the effect of NMDA (1 lM) and caused a rightward shift in the NMDA sensitivity. It was tested whether the antagonist effects were due to dopamine receptor blockade or increased tone on D 1 /D 2 receptors. SCH23390 prevented the raclopride-induced enhancement of spontaneous but not NMDA-evoked glutamate release while raclopride left unchanged the SCH23390-induced inhibition. The physiopathological relevance of the dopaminergic modulation was strengthened by perfusing NMDA in the dopaminedepleted striatum of hemiparkinsonian rats. Nigral glutamate responsiveness to NMDA was enhanced as with raclopride. We conclude that endogenous striatal dopamine regulates both spontaneous and NMDA-induced nigral glutamate release via an opposite control mediated by D 1 facilitatory and D 2 inhibitory receptors. Alterations of this control may subserve the motor symptoms of Parkinson's disease.

Blockade of Nociceptin/Orphanin FQ Receptor Signaling in Rat Substantia Nigra Pars Reticulata Stimulates Nigrostriatal Dopaminergic Transmission and Motor Behavior

“…Two concentric probes were stereotaxically implanted under isoflurane anesthesia in the right dorsolateral striatum (DLS) (3 mm length) and ipsilateral SNr (1 mm length), as described previously (Marti et al, 2002b). Forty-eight hours after surgery, the microdialysis probes were perfused at a flow rate of 3 l/min with a modified Ringer's solution (in mM: 1.2 CaCl 2 , 2.7 KCl, 148 NaCl, and 0.85 MgCl 2 ), and samples were collected every 15 min, starting 6 hr after the onset of probe perfusion.…”

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

“…Two weeks after surgery, rats were injected with amphetamine (5 mg/kg, i.p., dissolved in saline) and only those rats performing more than seven ipsilateral turns per minute were enrolled in the study. This behavior has been associated with Ͼ95% loss of striatal extracellular DA levels (Marti et al, 2002b). Experiments were performed 6 -8 weeks after lesion.…”

Blockade of Nociceptin/Orphanin FQ Transmission Attenuates Symptoms and Neurodegeneration Associated with Parkinson's Disease

“…Unilateral lesion of DA neurons (Marti et al, 2002b) was induced in isoflurane-anesthetized male Sprague Dawley rats (150 g; Harlan Italy, S. Pietro al Natisone, Italy). Eight micrograms of 6-OHDA (in 4 l of saline containing 0.2% ascorbic acid) were stereotaxically injected into the right SN [from bregma: anteroposterior (AP), Ϫ4.4 mm; mediolateral (ML), Ϫ1.2 mm; ventrodorsal (VD), Ϫ7.8 mm below dura (Paxinos and Watson, 1982)].…”

“…Two weeks after surgery, rats were injected with amphetamine (5 mg/kg, i.p., dissolved in saline just before use), and only those rats performing more than seven ipsilateral turns per minute were enrolled in the study. This behavior has been associated with Ͼ95% loss of striatal extracellular DA levels (Marti et al, 2002b). Experiments were performed 6 -8 weeks after lesion.…”