title: Fasting biases μ-opioid receptors toward β-arrestin2-dependent signaling in the accumbens shell.
abstract: The μ-opioid receptor (MOR) and dopamine D1receptor 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 D1receptor transduction system is observed. In mice, morphine administration induces hypermotility and this response has been described in terms of a β-arrestin2-dependent mechanism that favors prevalent dopamine D1receptor 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 D1receptors in striatal areas and we studied the effects of acute pharmacological MOR stimulation on motility and nucleus accumbens shell (NAcS) dopamine D1receptor signaling in control rats and rats with reduced β-arrestin2 expression in the NAcS, either non food-deprived (NFD) or FD. Motility and dopamine D1receptor signaling increased only in FD rats in a β-arrestin2-dependent way. Moreover, FD rats showed a β-arrestin2-dependent increase in the levels of MOR-dopamine D1receptor heteromeric complexes in the NAcS. Sucrose consumption is accompanied by release of endogenous opioids and dopamine in the NAcS. We then examined MOR-dopamine D1receptor interactions after sucrose consumption. Sucrose increased NAcS dopamine D1receptor signaling in NFD and FD rats, and a reduction in β-arrestin2 expression prevented this effect selectively in FD rats. These results show the β-arrestin2-dependent prevalence of dopamine D1receptor signaling in response to acute morphine or sucrose consumption elicited by food deprivation in rats.
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Scheggi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferrari
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pelliccia
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Devoto
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Maria Graziella
authors.initials: MG
authors.lastname: De Montis
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: carla.gambarana@unisi.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Gambarana
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D005508:Food Deprivation; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013395:Sucrose / Q000378:metabolism; D013549:Sweetening Agents / Q000494:pharmacology; D000071560:beta-Arrestin 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D001552:Benzazepines; D015259:Dopamine Agents; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D034741:RNA, Small Interfering; D017447:Receptors, Dopamine D1; D017450:Receptors, Opioid, mu; C534628:SCH 23390; D013549:Sweetening Agents; D000071560:beta-Arrestin 2; D013395:Sucrose; D009020:Morphine
keywords: dopamine D(1) receptors; dopamine and cAMP-regulated phosphoprotein of Mr 32000 (DARPP-32); morphine; rat; sucrose