title: Propofol decreases stimulated dopamine release in the rat nucleus accumbens by a mechanism independent of dopamine D2, GABAA and NMDA receptors.
abstract: Although propofol (2,6-di-isopropylphenol) is a popular i.v. general anaesthetic, it has been suggested to have abuse potential. As many drugs of abuse act preferentially via release of dopamine in the limbic system, we investigated the action of propofol on stimulated dopamine release in the rat nucleus accumbens. Nucleus accumbens slices were superfused (1.6 ml min-1) with artificial cerebrospinal fluid at 32 degrees C. Dopamine release was evoked by electrical stimulation (10 pulses, 0.1 ms, 10 mA, 10 Hz, every 10 min) and monitored by fast cyclic voltammetry. Propofol 100 mumol litre-1 reduced stimulated dopamine release over the 2 h after administration, relative to intralipid controls, to mean 30 (SEM 2)% (P < 0.01). The dopamine D2 receptor antagonist metoclopramide 0.3 mumol litre-1 increased dopamine release but did not block the effect of propofol (38 (3)%). The selective GABAA antagonist bicuculline 24 mumol litre-1 also failed to antagonize the action of propofol (45 (3)%). The NMDA receptor antagonist dextromethorphan 10 mumol litre-1 decreased dopamine release to 57 (6)% (P < 0.01) but failed to block the inhibitory effect of propofol (46 (6)%). Although propofol has been reported to bind to D2, GABAA and NMDA receptors, failure of metoclopramide and bicuculline to block its effects suggests that an agonist action at D2 or GABAA receptors does not mediate the effects of propofol on dopamine release in the rat nucleus accumbens. The lack of effect of dextromethorphan makes an NMDA receptor antagonist action unlikely.
authors.affiliation: Department of Anaesthesiology, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Schulte
authors.forename: L F
authors.initials: LF
authors.lastname: Callado
authors.forename: C
authors.initials: C
authors.lastname: Davidson
authors.forename: P E
authors.initials: PE
authors.lastname: Phillips
authors.forename: N
authors.initials: N
authors.lastname: Roewer
authors.forename: J
authors.initials: J
authors.lastname: Schulte am Esch
authors.forename: J A
authors.initials: JA
authors.lastname: Stamford
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
chemical_list: D018686:Anesthetics, Intravenous; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D004298:Dopamine; D015742:Propofol