Kappa opioid receptors in the rostral ventromedial medulla of male and female rats

Abstract

Kappa opioid receptor (KOR) ligands alter nociceptive responses when applied to the rostral ventromedial medulla (RVM). However, the effects of kappa opioid receptor ligands are distinct in males and females. The present study examined the distribution of kappa opioid receptor immunoreactivity in the RVM of male and female rats. KOR immunoreactivity was found at pre- and postsynaptic sites within the RVM of both sexes. The most common KOR-immunoreactive (KOR-ir) neuronal structures were unmyelinated axons, followed by axon terminals, dendrites, and somata. Different proportions of KOR-ir axon terminals and dendrites were found in females at different estrous stages. Specifically, dendrites containing KOR immunoreactivity were less abundant in proestrus females compared with estrus females and showed a trend toward being less abundant in males, suggesting that KOR ligands applied to the RVM may be less potent in proestrus females. These findings suggest that the distribution of KORs in the RVM may be influenced by reproductive hormone levels. We also found KOR immunoreactivity in many spinally projecting neurons within the RVM of female rats. These findings are consistent with the hypothesis that KOR ligands influence nociceptive behaviors by altering the activity of specific populations of neurons within the RVM. The abundance of KOR in axons and axon terminals in RVM indicates a substantial role for presynaptic effects of KOR ligands through pathways that have not been clearly delineated. Altering the balance between pre- and postsynaptic receptive sites may underlie differences in the effects of KOR agonists on nociceptive responses in males and females.

Morphine- and CaMKII-Dependent Enhancement of GIRK Channel Signaling in Hippocampal Neurons

“…DPDPE (100 µm), a selective agonist for δ–opioid receptor, also did not significantly change the colocalization of GIRK2 and PSD-95 (Table 1). By contrast, hippocampal neurons exposed for ~20 h to 10 and 30 µm met-enkephalin, which stimulates μ- and δ–opioid receptors (Drake et al, 2007b), increased the colocalization ratio for GIRK2 and PSD95 (Figure 2F), similar to morphine. Most common opioid receptors couple to PTX-sensitive G proteins.…”

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).…”

In vivo trafficking of endogenous opioid receptors

“…The efficacy of U69,593 was significantly enhanced in animals that had chronic inflammatory pain induced by hind paw injection of complete Freund's adjuvant. The presence of KOPR in rostral ventromedial medulla has been reported (Drake et al 2007). Whether the enhanced efficacy of U69,593 is due to the increase in the number of cell surface KOPR and/or down-stream signaling needs further investigation.…”