Abstract
In rat hippocampal slices, opioids potentiate the synaptic activation of pyramidal neurons as revealed by the shift to the left in the input-output curve constructed by plotting the population spike as a function of the field EPSP. The peak effect was obtained within 12–25 min with D-Ala 2, D-Leu 5-enkephalin (DADLE), morphiceptin and morphine. However, the effect of both peptides declined during constant superfusion. About 60% peak effect was lost after 1 hr superfusion with morphiceptin or after 4 hr with DADLE. In contrast, the effect of morphine gradually increased over a 4 hr incubation. Following superfusion of the slices for 4 hr in DADLE or morphine, or 1.5 hr in morphiceptin, the membrane particulate fractions were prepared from the homogenate of slices. Opiate receptor binding activities were measured with 125I-DADLE (δ-receptors) and 125I-FK 33824 (μ-receptors). A significant reduction in δ- but not μ-receptor binding was detected in slices treated with DADLE. This seems to correlate to the development of desensitization to DADLE. Neither μ-receptor nor δ-receptor binding activity was altered by the superfusion of morphine or morphiceptin despite the development of desensitization to morphiceptin. These data suggest that there are differences in the regulation of μ- and δ-receptors in hippocampus. The down-regulation of δ-receptors may result in desensitization to δ-agonists and a different mechanism may be responsible for desensitization to μ-agonists.
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