Kappa opioid receptor-like immunoreactivity is present in substance P-containing subcortical afferents in guinea pig dentate gyrus

Abstract

We have previously shown that kappa opioid receptor‐like immunoreactivity (KT‐LI) is present in axons and terminals in the granule cell layer and inner molecular layer of the guinea pig dentate gyrus. The distribution and ultrastructural appearance of processes with KT‐LI were similar to those of the substance P (SP)‐containing afferents which arise from the supramammillary region of the hypothalamus (SUM) and enter the hippocampal formation through the fimbria‐fornix. The objective of the present study was to determine whether the terminals with KT‐LI are likely to be SUM afferents. To accomplish this we 1) compared the intensity of KT‐ and SP‐immunolabeling in the dentate gyrus ipsilateral and contralateral to a unilateral fornix transection and 2) used dual‐labeling electron microscopy to determine whether terminals with KT‐LI colocalize SP‐LI in the dentate gyrus. Light microscopic examination of the dentate gyrus demonstrated that KT‐LI and SP‐LI were in thin processes with overlapping distributions in strata granulosum and moleculare. Following fornix transection, both KT‐LI and SP‐LI were dramatically reduced in these regions of the dentate gyrus ipsilateral to the transection, consistent with an SUM origin. By electron microscopy, most (71%) terminals with KT‐LI also contained detectable SP‐LI in single‐section analysis. Many dual‐labeled terminals formed thick asymmetric synaptic contacts with large dendritic shafts (2–5 μm) or granule cell perikarya, and a smaller proportion contacted dendritic spines; these characteristics resembled those of identified SUM afferents in other species. The demonstrations that 1) KT‐LI colocalizes with SP‐LI in a morphologically distinctive population of axon terminals and 2) most of the processes with KT‐LI enter through the fimbria‐fornix suggest that kappa opioid receptors are present in the SUM projection to the dentate gyrus. Hippocampus 7:36–47, 1997. © 1997 Wiley‐Liss, Inc.

Cellular Sites for Dynorphin Activation of κ-Opioid Receptors in the Rat Nucleus Accumbens Shell

“…These data indicate that KOR and Dyn may be transported to functional sites under similar conditions (Schwarzenbrunner et al, 1990;Drake et al, 1996). Dually labeled terminals were large and formed symmetric synapses with dendrites, consistent with the localization of KOR to Dyn-containing neurons containing substance P or GABA (Pickel et al, 1988;Van Bockstaele et al, 1995;Drake et al, 1997a). These data suggest that KOR may be a presynaptic autoreceptor, regulating the release of Dyn or other transmitters (Gannon and Terrian, 1991).…”

Opioid Modulation of Recurrent Excitation in the Hippocampal Dentate Gyrus

“…In vivo experiments in rats have demonstrated a potentiation of perforant path excitation by this pathway and a correlation in activity with dentate theta rhythm (Segal, 1979;Dahl and Winson, 1986;Carre and Harley, 1991). Evidence that supramammillary afferents contain immunoreactivity for opiate receptors (Drake et al, 1997) gives credence to the idea that this pathway is also under dynorphin control and underscores the importance of dynorphin modulation of excitability in guinea pig dentate gyrus. Nevertheless, it is not clear that stimulation of only the hilus (and not the perforant path) would activate these supramammillary afferents consistently and selectively as seen in the present hilar stimulation studies.…”

Agonist-induced internalization of kappa-opioid receptors in noradrenergic neurons of the rat locus coeruleus

“…Blots incubated with 1.5 μg/ml of affinity-purified κOR antiserum preincubated with antigenic peptide did not show any bands. The κOR antibody specificity was also demonstrated by κOR immunoreactivity in the forebrain and pons (Drake et al, 2007; Drake et al, 1997; Drake et al, 1996) and spinal cord (Wang et al, 2009). We previously reported κOR specificity by using HEK293 cells transiently transfected with pcDNA3-FLAG-rat κOR and double labeled with the M2 monoclonal antibody against FLAG where a consistent identical staining was observed indicating that the antibody used recognizes κOR (Reyes et al, 2009; Wang et al, 2009).…”