FASTING BIASES μ-OPIOID RECEPTORS TOWARD B-ARRESTIN2-DEPENDENT SIGNALING IN THE ACCUMBENS SHELL

The mu-opioid receptor (MOR) and dopamine D-1 receptor are co-expressed in the medium spiny neurons of striatal areas and the signaling pathways activated by these two receptors are in functional competition. However, in certain conditions an integrated response mediated by the dopamine D-1 receptor transduction system is observed. In mice, morphine administration induces hypermotility and this response has been described in terms of a beta-arrestin2-dependent mechanism that favors prevalent dopamine D-1 receptor activation. In rats, acute morphine administration induces hypermotility only when the animals are food-deprived (FD). We aimed to further investigate the functional interaction between the MOR and dopamine D-1 receptors in striatal areas and we studied the effects of acute pharmacological MOR stimulation on motility and nucleus accumbens shell (NAcS) dopamine D-1 receptor signaling in control rats and rats with reduced beta-arrestin2 expression,in the NAcS, either non food-deprived (NFD) or FD. Motility and dopamine D-1 receptor signaling increased only in FD rats in a beta-arrestin2-dependent way. Moreover, FD rats showed a beta-arrestin2-dependent increase in the levels of D-1 receptor heteromeric complexes in the NAcS. Sucrose consumption is accompanied by release of endogenous opioids and dopamine in the NAcS. We then examined MOR-dopamine D-1 receptor interactions after sucrose consumption. Sucrose increased NAcS dopamine D-1 receptor signaling in NFD and FD rats, and a reduction in beta-arrestin2 expression prevented this effect selectively in FD rats. These results show the beta-arrestin2-dependent prevalence of dopamine D-1 receptor signaling in response to acute morphine or sucrose consumption elicited by food deprivation in rats. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.