title: Self-administration of propofol is mediated by dopamine D1 receptors in nucleus accumbens in rats.
abstract: As a widely used intravenous short-acting anesthetic, propofol is recently indicated by clinical and animal studies for its abuse potential, but the mechanism underlying propofol abuse is largely unknown. This study examined the contribution of dopamine receptor subtype (D1 and D2 receptors) and neuroanatomical locus (i.e. nuclear accumbens) in the maintenance of propofol self-administration in rats. After the acquisition and maintenance of self-administration of propofol (1.7 mg/kg/infusion) under a fixed ratio (FR1) schedule of reinforcement over 14 days, rats were treated by either intraperitoneal injection or intra-nucleus accumbens (NAc) injection of D1 receptor antagonist (SCH23390) or D2 receptor antagonists (spiperone and eticlopride) 10 min prior to the subsequent propofol self-administration. We demonstrated (i) systemic administration of SCH23390 (10, 30, 100 μg/kg, i.p.) dose-dependently decreased the rate of propofol-maintained self-administration, suggesting a critical role of the D1 receptor in mediating propofol self-administration; (ii) the blockade of the propofol self-administration by SCH23390 was specific since spiperone and eticlopride did not affect propofol self-administration and SCH23390 at these doses did not affect food-maintained responding under an FR5 schedule; (iii) intra-accumbenal injection of SCH23390 (2.5 μg/site) but not eticopride (3.0 μg/site) attenuated the propofol self-administration, localizing nuclear accumbal D1 receptors as a critical locus in the reinforcement of propofol. Together, these findings provide the first direct evidence that D1 receptors in nuclear accumbens play an important role in the maintenance of propofol self-administration.
authors.affiliation: Department of Anesthesiology of the 2nd Affiliated Hospital and Institute of Neuroendocrinology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Lian
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Jin
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: Q
authors.initials: Q
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Lai
authors.forename: K
authors.initials: K
authors.lastname: Lu
authors.forename: L
authors.initials: L
authors.lastname: Tang
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: J-F
authors.initials: JF
authors.lastname: Chen
authors.forename: R-S
authors.initials: RS
authors.lastname: Ge
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D015742:Propofol / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012457:Salicylamides / Q000494:pharmacology; D012646:Self Administration; D013134:Spiperone / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D006993:Hypnotics and Sedatives; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D012457:Salicylamides; D013134:Spiperone; C045989:eticlopride; D015742:Propofol