title: Uridine decreases morphine-induced behavioral sensitization by decreasing dorsal striatal dopamine release possibly via agonistic effects at GABAA receptors.
abstract: Uridine, a potential endogenous neuromodulator, has been demonstrated to interact with the dopaminergic system and to regulate dopamine-related behaviors. The present study investigated the effects of uridine on morphine-induced hyperactivity and behavioral sensitization and on modulating dopaminergic neurotransmission in mice, which may help to understand how uridine and its metabolites act as modulators of the GABAA receptors. The results showed that either systemic (30 or 100mg/kg) or central (30, 100 or 300nM) uridine administration significantly attenuated the hyperactivity induced by acute morphine treatment in mice. Intracerebroventricular administration of uracil and β-alanine also inhibited morphine-induced hyperactivity. Uridine, a known modulator of the GABA receptors, increased the extracellular levels of GABA in the brain. In addition, the GABAA receptors antagonist bicuculline significantly attenuated the effects of uridine on morphine-induced hyperactivity, suggesting that the GABAA receptors potentially mediate the effects of uridine and its metabolites on morphine-related activity. It was also observed that morphine-induced locomotor sensitization was abolished after chronic uridine treatment. In vivo microdialysis demonstrated that uridine reversed morphine-induced dopamine release in the dorsal striatum of morphine-sensitized mice. In conclusion, these data suggest that the therapeutic effects of uridine and its metabolites on morphine-induced hyperactivity and established behavioral sensitization may be mediated in part by interfering with the dopaminergic system possibly via agonistic effects at GABAA receptors.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Wu
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Mathematics Teaching & Research Section, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Rongwu
authors.initials: R
authors.lastname: Xiang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: yangjingyu2006@gmail.com.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Yang
mesh_terms: D000701:Analgesics, Opioid / Q000633:toxicity; D000818:Animals; D017849:Animals, Inbred Strains; D001640:Bicuculline / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy* / Q000209:etiology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D011963:Receptors, GABA-A / Q000378:metabolism*; D013997:Time Factors; D014498:Uracil / Q000494:pharmacology; D014529:Uridine / Q000627:therapeutic use*; D015091:beta-Alanine / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D015091:beta-Alanine; D014498:Uracil; D009020:Morphine; D004298:Dopamine; D014529:Uridine; D001640:Bicuculline
keywords: Dopamine; Dorsal striatum; Microdialysis; Morphine; Uridine; β-alanine