Agonists of the alpha-2A-adrenergic- (alpha(2A)-AR) and the mu-opioid-receptor (muOR) jointly affect autonomic functions that are also disregulated in animals undergoing withdrawal from chronic administration of the muOR agonist morphine. Cardiovascular and gastrointestinal reflexes are mediated, in part, by the medial nucleus of the solitary tract (mNTS) at caudal (cNTS) and intermediate (iNTS) subregions. Together, this evidence suggests that alpha(2A)-AR and muOR may be colocalized within many of the same neuronal profiles in both the intermediate and caudal mNTS. In order to examine whether alpha(2A)-AR and muOR are present within common somata, dendrites, or axon terminals in the mNTS, we used electron microscopic immunocytochemistry for the detection of antisera against each receptor at intermediate and caudal levels of this brain region. Most of the dually labeled profiles were somata and dendrites. Of all dual-labeled profiles in the iNTS 49% were somata and were 47% dendrites, whereas in the cNTS 61% were somata and 32% were dendrites. Within dual-labeled profiles, the intracellular distribution of alpha(2A)-AR and muOR differed. MuOR was more frequently associated with the plasmalemma, whereas alpha(2A)-AR was often affiliated with vesicular organelles. Few axon terminals, and even fewer glia, contained both markers. We also frequently observed single-labeled alpha(2A)-AR glia that apposed exclusively muOR-containing dendrites or axon terminals. These findings indicate that somata and dendrites contain functional sites for convergent muOR and alpha(2A)-AR activation. In addition, each receptor is positioned for involvement in intercellular signaling between apposed neurons and glia. Activation of alpha(2A)-AR on muOR-containing somata or dendrites, or on glia apposed to muOR-containing neurons, may help to account for the efficacy of alpha(2A)-AR agonists in relieving some of the autonomic symptoms of opiate withdrawal.
Copyright 2002 Wiley-Liss, Inc.