Influence of glial cells in the dopamine releasing effect resulting from the stimulation of striatal delta-opioid receptors.
Recent data indicate that striatal dopamine release induced by stimulation of delta-opioid receptors is a consequence of glutamate release. However, glial cells, which mainly support glutamate uptake and are involved in glutamate signaling and potentially express delta-opioid receptors, could participate to this effect. The present study investigates the contribution of glial cells in the releasing effects of [d-Pen2, d-Pen5]-enkephalin (DPDPE) by using the gliotoxin l-alpha-aminoadipate (l-alpha AA). Initially, we evaluated the early influence of l-alpha AA local infusion (10 microg/microL) on dialysate levels of glutamate and dopamine under basal or DPDPE treatment conditions. l-alpha AA produced a significant increase of glutamate and dopamine in dialysates (+76% and +50% respectively) and the concomitant infusion of DPDPE (10 microM) significantly enhanced this effect in an additive manner (+110% and +44% respectively). Secondly, we assessed the DPDPE effects on striatal glutamate and dopamine dialysate levels, 2 days after an intra-striatal injection of l-alpha AA which produced destruction of glial cells. This lesion, decreasing the basal glutamate dialysate level as well as its tissue content (by 55% and 36% respectively), prevented the increase in glutamate and dopamine extracellular levels induced by DPDPE. This result confirmed that the DPDPE-induced dopamine release requires an initial glutamate release. However, this effect could reflect a major disruption of glutamatergic transmission caused by the toxin, as suggested by the local infusion of glutamine (2.5 mM) which, in lesioned rats, prevented the decrease in the basal extracellular content of glutamate and restored the DPDPE-induced increase in glutamate and dopamine dialysate levels. Therefore, these results indicate that, although glial cells are essential to maintain functional glutamatergic neurotransmission, they are not directly involved in the process by which stimulation of striatal delta-opioid receptors induces extracellular glutamate release and, consecutively, dopamine release.
Billet
F
F
Unité de Neuropsychopharmacologie Expérimentale, F.R.E. 2735 C.N.R.S., Institut Hospitalo-Universitaire de Recherche Biomédicale, I.F.R.M.P. no.23, Faculté de Médecine et de Pharmacie de Rouen, 22 Boulevard Gambetta, 76183 Rouen cedex 01, France.
Costentin
J
J
Dourmap
N
N
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D018377:Neurotransmitter Agents; D017465:Receptors, Opioid, delta; D015074:2-Aminoadipic Acid; D018698:Glutamic Acid; D020881:Enkephalin, D-Penicillamine (2,5)-; D005974:Glutamate-Ammonia Ligase; D004298:Dopamine