Involvement of cholinergic neurons in the release of dopamine elicited by stimulation of mu-opioid receptors in striatum

The involvement of striatal cholinergic neurons in the release of dopamine (DA) elicited by the mu-opioid receptor agonist DAGO ([D-Ala(2), NMePhe(4)-Gly(5)(ol)]enkephalin) was explored. The striatal release of DA was measured by microdialysis in rats anesthetized with chloral hydrate. When infused in the striatum, through the microdialysis probe, DAGO increased the extracellular levels of DA. The previous injection in striatum of AF 64-A, a toxin for cholinergic neurons, or the concomitant infusion of the M(2)-muscarinic antagonist methoctramine abolished the effect of DAGO on the DA release. It is concluded that stimulation of mu-opioid receptors, by inhibiting the acetylcholine release which stimulates tonically M(2)-muscarinic receptors likely associated with dopaminergic nerve endings, indirectly increases the striatal DA release.