title: Corticotropin-releasing factor 1 receptor mediates the activity of the reward system evoked by morphine-induced conditioned place preference.
abstract: Different neurotransmitter systems are involved in behavioural and molecular responses to morphine. The brain stress system is activated by acute administration of drugs of abuse, being CRF the main neuropeptide of this circuitry. In this study we have studied the role of CRF1R in the rewarding effects of morphine using the CPP paradigm. For that, animals were treated with a CRF1R antagonist (CP-154,526) or vehicle during 6 days. Thirty min after receiving the antagonist, mice were injected with morphine on the same days that CP-154,526 was administered; another group received saline on the same days that vehicle was administered, and both groups were immediately conditioned. Control animals received vehicle and saline every day. On day 7, animals were tested for morphine-induced CPP. c-Fos, TH and OXA immunohistochemistry, NA turnover (HPLC), and corticosterone plasma concentration (RIA) were evaluated. Administration of a CRF1R antagonist CP-154,526 blocked the morphine-induced CPP and the increased NA turnover in the NAc in morphine-paired mice. CP-154-526 antagonised the enhancement in c-Fos expression evoked by morphine-induced CPP in the VTA and NAc, and the activation of the orexinergic neurons in the LLH. Present work demonstrates that morphine-induced CPP activates different brain areas involved in reward, and points out a critical role of CRF1R in molecular changes involved in morphine-conducted behaviours. Thus, our study supports a therapeutic potential of CRF1R antagonists in addictive disorders.
authors.affiliation: Group of Cellular and Molecular Pharmacology, Faculty of Medicine, University of Murcia, Spain; IMIB (Institute of Biomedical Investigation of Murcia)-Arrixaca, Murcia, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Lasheras
authors.affiliation: Group of Cellular and Molecular Pharmacology, Faculty of Medicine, University of Murcia, Spain; IMIB (Institute of Biomedical Investigation of Murcia)-Arrixaca, Murcia, Spain.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Laorden
authors.affiliation: Group of Cellular and Molecular Pharmacology, Faculty of Medicine, University of Murcia, Spain; IMIB (Institute of Biomedical Investigation of Murcia)-Arrixaca, Murcia, Spain.
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Milanés
authors.affiliation: Group of Cellular and Molecular Pharmacology, Faculty of Medicine, University of Murcia, Spain; IMIB (Institute of Biomedical Investigation of Murcia)-Arrixaca, Murcia, Spain. Electronic address: crisnp@um.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Núñez
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011897:Random Allocation; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology; D000099052:CRF Receptor, Type 1
chemical_list: C101628:CP 154526; D006727:Hormone Antagonists; D009294:Narcotics; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D009020:Morphine
keywords: CRF1R; Catecholamine; Conditioned place preference; Corticosterone; LC; Morphine; NAc; NTS-A2; Orexins; VTA