Effect of selective opiate antagonists on striatal acetylcholine and dopamine release

We investigated the effect of selective opiate antagonists on striatal acetylcholine (ACh) and dopamine (DA) release. The mu-receptor antagonist beta-funaltrexamine (beta-FNA), the delta-antagonist naltrindole (NTI), and the kappa-antagonist norbinaltorphimine (nor-BNI) were used to selectively block different subtypes of opiate receptors. The experiments were carried out on isolated superfused striatal slices of rats, loaded with [3H]choline or [3H]dopamine. beta-FNA and NTI significantly enhanced the electrical field stimulation-evoked release of ACh but only if the dopaminergic input had been impaired either by chemical denervation or D2 dopamine receptor blockade. By contrast, neither the selective nor nonselective antagonists had any modulatory effect on the release of dopamine. It is concluded, therefore, that the release of ACh is tonically controlled by endogenous opioid peptide(s) through the stimulation of mu- and delta-opiate receptors located on cholinergic axon terminals, in addition to the tonic control by DA.