High-affinity neurotensin receptors in the rat nucleus accumbens: Subcellular targeting and relation to endogenous ligand

Neurotensin is present in selective mesolimbic dopaminergic projections to the nucleus accumbens (NAc) shell but also is synthesized locally in this r egion and in the motor-associated NAc core. We examined the electron micros copic immunolabeling of the high-affinity neurotensin receptor (NTR) and ne urotensin in these subdivisions of rat NAc to determine the sites for recep tor activation and potential regional differences in distribution. Througho ut the NAc, NTR immunoreactivity was localized discretely within both neuro ns and glia. NTR-labeled neuronal profiles were mainly axons and axon termi nals with diverse synaptic structures, which resembled dopaminergic and glu tamatergic afferents, as well as collaterals of inhibitory projection neuro ns. These terminals had a significantly higher numerical density in the NAc core than in the shell but were prevalent in both regions, suggesting invo lvement in both motor and limbic functions. In each region, neurotensin was detected in a few NTR-immunoreactive axon terminals and in terminals that formed symmetric, inhibitory type synapses with NTR-labeled somata and dend rites. The NTR labeling, however, was not seen within these synapses and, i nstead, was localized to segments of dendritic and glial plasma membranes o ften near excitatory type synapses. Neuronal NTR immunoreactivity also was associated with cytoplasmic tubulovesicles and nuclear membranes. Our resul ts suggests that, in the NAc shell and core, NTR is targeted mainly to pres ynaptic sites, playing a role in the regulated secretion and/or retrograde signaling in diverse, neurotransmitter-specific neurons. The findings also support a volume made of neurotensin actions, specifically affecting excita tory transmission through activation of not only axonal but also dendritic and glial NTR. (C) 2001 Wiley-Liss, Inc.