κ Opioid receptor activation in different brain regions differentially modulates anxiety-related behaviors in mice

kappa Opioid receptor system is widely implicated in the regulation of emotion. However, the findings about the role on anxiety in rodents are highly controversial, since both anxiogenic- and anxiolytic-like effects have been reported with kappa opioid receptor activation. The mechanism and the underlying neuroanatomical substrates are unexplored. In the present study, we first investigated the effects of kappa agonist U50,488H on anxiety-related behaviors over a wide range of doses, and we found that U50,488H produced dual effects in anxiety, with low dose being anxiogenic and high dose being anxiolytic. To assess the potential neuroanatomical substrates, we used phosphorylation of extracellular signal-related kinasel /2 (pERK1/2) to map the underlying neural circuits. We found that the anxiogenic effect of U50,488H was paralleled by an increase of pERK1/2 in the nucleus accumbens, whereas the anxiolytic effect was paralleled by an increase of pERK1/2 in the lateral septa] nucleus. We then examined the behavioral consequences with locally microinjection of U50,488H, and we found that microinjection of U50,488H into the nucleus accumbens exerted anxiogenic-like effects, whereas microinjection of U50,488H into the lateral septa] nucleus. Both effects can be abolished by kappa antagonist nor-BNI pretreatment. To the best of our knowledge, the present work firstly provides the neuroanatomical sites that mediating the dual anxiogenic- and anxiolytic-like effects of U50,488H in mice. This study may help to explain current controversial role of kappa receptor activation in anxiety-related behaviors in rodents, and may open new perspectives in the areas of anxiety disorders and K receptor function. (C) 2016 Elsevier Ltd. All rights reserved.