The goal of this proposal is to investigate the regulation by kappa and delta opioid receptors of striatal glutamate efflux in synaptosomes using NADPH-linked fluorometry. Psychostimulant-induced motor activity is blocked by glutamate receptor antagonists and by kappa opioid receptor agonists and delta opioid receptor antagonists. Because the striatum is a locus for psychostimulant-induced behavioral effects and kappa and delta opioid receptors are expressed there, the structure is ideal for investigating opioid-glutamatergic interactions. The first objective of this proposal is to determine whether striatal glutamate efflux is regulated by presynaptic kappa opioid receptors. Kappa opioid receptor activation decreases L-trans-PDC-evoked striatal glutamate levels in vivo and 4-AP-evoked glutamate efflux in synaptosomes. Therefore, we will compare the effects of kappa receptors activation on glutamate efflux evoked by L-trans-PDC and 4-AP. The second objective of this proposal is to determine whether glutamate efflux is regulated by presynaptic delta opioid receptors. Because cholinergic interneurons express delta opioid receptor MRNA and muscarinic agonists decrease striatal glutamate release, we expect that blockade of delta receptors will reduce glutamate efflux by increasing acetylcholine release from presynaptic loci. These studies will contribute information about the regulation by opioid receptors of glutamate efflux in the striatum. Data generated by these studies will provide insight into the role of opioid systems in the modulation of glutamate levels which underlie the actions of psychostimulants.
