Presynaptic Versus Postsynaptic Localization of μ and δ Opioid Receptors in Dorsal and Ventral Striatopallidal Pathways

Abstract

Parallel studies have demonstrated that enkephalin release from nerve terminals in the pallidum (globus pallidus and ventral pallidum) can be modulated by locally applied opioid drugs. To investigate further the mechanisms underlying these opioid effects, the present study examined the presynaptic and postsynaptic localization of ␦ (DOR1) and (MOR1) opioid receptors in the dorsal and ventral striatopallidal enkephalinergic system using fluorescence immunohistochemistry combined with anterograde and retrograde neuronal tracing techniques. DOR1 immunostaining patterns revealed primarily a postsynaptic localization of the receptor in pallidal cell bodies adjacent to enkephalin-or synaptophysin-positive fiber terminals. MOR1 immunostaining in the pallidum revealed both a presynaptic localization, as evidenced by punctate staining that co-localized with enkephalin and synaptophysin, and a postsynaptic localization, as evidenced by cytoplasmic staining of cells that were adjacent to enkephalin and synaptophysin immunoreactivities. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) or the retrograde tracer Texas Red-conjugated dextran amine (TRD) into the dorsal and ventral striatum resulted in labeling of striatopallidal fibers and pallidostriatal cell bodies, respectively. DOR1 immunostaining in the pallidum co-localized only with TRD and not PHA-L, whereas pallidal MOR1 immunostaining co-localized with PHA-L and not TRD. These results suggest that pallidal enkephalin release may be modulated by opioid receptors located presynaptically on striatopallidal enkephalinergic neurons and by ␦ opioid receptors located postsynaptically on pallidostriatal feedback neurons.

Estrogen-Induced Alteration of μ-Opioid Receptor Immunoreactivity in the Medial Preoptic Nucleus and Medial Amygdala

“…Preabsorption of the -OR antiserum with the synthetic peptide fragment used to generate antibodies prevented immunostaining in tissue specimens and has previously been reported (Sternini et al, 1996;Olive et al, 1997). Moreover, the appearance and distribution of -ORi in this study is similar to the distribution Mansour et al…”

“…After etorphine treatment, the number of cell bodies and processes in which the -ORi was localized within the structure was dramatically increased. In these structures, the immunoreactivity was not associated with the plasma membrane but was localized within processes in a pattern that is consistent with internalized receptors (Mantyh et al, 1995a,b;Sternini et al, 1996;Allen et al, 1997;Olive et al, 1997;Keith et al, 1998). This pattern of receptor internalization was correlated at the light microscopic level with an increase in the density of distinct varicose fibers throughout the brain, including the cortex, the globus pallidus, thalamus, lateral hypothalamus, and central amygdala.…”

The glutamatergic projection from the prefrontal cortex to the nucleus accumbens core is required for cocaine-induced decreases in ventral pallidal GABA

“…One of these adaptations is reduced GABA in the VP, and this cocaine-induced reduction is blocked by inhibiting mu opioid receptors in the VP [20]. It has long been known that GABA and enkephalin co-localize in the NAcore to VP projection, and the effect of mu opioid receptor blockade indicates that co-released enkephalin may be presynaptically inhibiting GABA release [14,15,20]. A final consideration is that the source of extracellular GABA in the VP is not well defined, and may arise from the NAcore afferents, recurrent collaterals from the GABAergic VP projection neurons, or from non-neuronal sources.…”

μ Opioid receptor A118G polymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers

“…The opposing effects of acute heroin intake on the opioid neuropeptide transcription levels in our study indicate a differential regulation of PENK and PDYN striatal gene expression by heroin. However, MORs are situated on both PDYN and PENK medium spiny projection striatal neurons (17,33), suggesting that other neural systems such as dopamine, which differentially regulates striatal PDYN and PENK, might contribute to the differential opioid neuropeptide effects (34).…”