Dopaminergic system mediates only delta-opiate inhibition of endogenous acetylcholine release evoked by glutamate from rat striatal slices.

In order to study the role of the dopaminergic system in the mu- or delta-opioid inhibition of endogenous acetylcholine release evoked by glutamate, we blocked the dopaminergic transmission with dopaminergic antagonists and/or 6-hydroxydopamine lesions. In all these experimental conditions we show that dopaminergic antagonists by themselves could not modify the glutamate-evoked acetylcholine release, and the selective D1 antagonist (SCH 23390) was unable to modify the mu- or delta-opioid inhibition of glutamate-evoked acetylcholine release. However, in the non-lesioned animals and in the contralateral striata to 6-hydroxydopamine lesions, D2 antagonists (haloperidol or sulpiride, 10 microM) prevented the effects of delta-opiate agonists ([D-Ala2, D-Leu5]enkephalin, 1 microM and [D-Pen2, D-Pen5]enkephalin, 0.1 microM), but not the effects of mu-opiate agonists (morphine or [D-Ala2, Gly(ol)5]enkephalin, 1 microM). Furthermore, [D-Ala2, D-Leu5]enkephalin inhibition of glutamate-evoked acetylcholine release was prevented by D2 antagonists in a concentration-dependent manner. Instead, in the 6-hydroxydopamine-lesioned side, while [D-Ala2, D-Leu5]enkephalin (1 microM) inhibition of glutamate-evoked acetylcholine release was completely abolished, morphine (1 microM) inhibition remained unchanged. We conclude that the inhibition of glutamate-evoked endogenous acetylcholine release by delta-opiate agonists, unlike mu-opiate agonists, depends on dopaminergic terminals and D2 receptors. Furthermore, these results suggest that the inhibition by delta-opiate agonists could be the result of dopamine release from dopaminergic terminals and its action on D2 receptors.