Opioid regulation of CNS dopaminergic pathways: a review of methodology, receptor types, regional variations and species differences

Biochemical measurements of DOPAC, HVA, DA and 3-MT allow the assessment of both DA metabolism in nerve endings and DA release into the synaptic cleft. Using these biochemical indices of DA neuronal activity, we have examined the actions of mu, delta and kappa opiate receptor agonists on the nigrostriatal pathway. These studies indicate that delta and mu2 isoreceptors regulate activity in the nigrostriatal pathway of the rat, mouse, gerbil and hamster. In general, increased DA metabolism is observed; however, increased DA release is only evident in pathways devoid of a presynaptic clamping action. As indicated with enkephalinase inhibitors, these enkephalinergic inputs to dopaminergic neurons possess a phasic ongoing activity.