kappa-Opioid inhibition of [3H]dopamine release from rat ventral mesencephalic dissociated cell cultures

The present study investigated the effect of opioids on [3H]dopamine release from mixed neuronal-glial cell cultures of embryonic rat ventral mesencephalon. Each of the major morphological types of dopaminergic cell was represented in these cultures. These cells exhibited specific uptake of [3H]dopamine, which was subsequently released, in a calcium-dependent manner, in response to a double pulse of elevated extracellular potassium. Spontaneous and potassium-evoked [3H]dopamine release was inhibited by kappa- but not mu- or delta-opioid agonists. The selective kappa 1 agonist (5 alpha, 7 alpha, 8 beta)-(-)-N-methyl-N-[7-(1-pyrollidinyl)-1-oxaspiro(4,5)- dec-8-yl]benzeneacetamide (U69593) produced a dose-dependent inhibition of dopamine release. The effect of U69593 was blocked by the nonselective opiate antagonist naloxone and the selective kappa opioid antagonist norbinaltorphimine. kappa-Opioid inhibition of potassium-evoked [3H]dopamine release was maintained in the presence of tetrodotoxin. These results suggest that functional kappa receptors, modulating dopamine release, are localized on the terminals of dopaminergic neurons.