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

Abstract

In order to study the role of the dopaminergic system in the μ- or δ-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 D 1 antagonist (SCH 23390) was unable to modify the μ- or δ-opioid inhibition of glutamate-evoked acetylcholine release. However, in the non-lesioned animals and in the contralateral striata to 6-hydroxydopamine lesions, D 2 antagonists (haloperidol or sulpiride, 10 μM) prevented the effects of δ-opiate agonists ([ d-Ala 2, d-Leu 5]enkephalin, 1 μM and [ d-Pen 2, d-Pen 5]enkephalin, 0.1 μM), but not the effects of μ-opiate agonists (morphine or [ d-Ala 2, Gly(ol) 5]enkephalin, 1 μM). Furthermore, [ d-Ala 2, d-Leu 5]enkephalin inhibition of glutamate-evoked acetylcholine release was prevented by D 2 antagonists in a concentration-dependent manner. Instead, in the 6-hydroxydopamine-lesioned side, while [ d-Ala 2, d-Leu 5]enkephalin (1 μM) inhibition of glutamate-evoked acetylcholine release was completely abolished, morphine (1 μM) inhibition remained unchanged. We conclude that the inhibition of glutamate-evoked endogenous acetylcholine release by δ-opiate agonists, unlike μ-opiate agonists, depends on dopaminergic terminals and D 2 receptors. Furthermore, these results suggest that the inhibition by δ-opiate agonists could be the result of dopamine release from dopaminergic terminals and its action on D 2 receptors.