title: The serotonin/noradrenaline reuptake inhibitor venlafaxine attenuates acquisition, but not maintenance, of intravenous self-administration of heroin in rats.
abstract: Opioids and antidepressants are frequently used for the treatment of various pain conditions. A combination of both drug classes may be more effective than either treatment alone, and combined treatment with an antidepressant may result in an opiate-sparing effect. Although it has been shown that antidepressants can attenuate self-administration of psychomotor stimulant and depressant drugs, it is not known whether they also attenuate self-administration of opiates. To determine whether venlafaxine, a serotonin/noradrenaline reuptake inhibitor with antidepressive and analgesic properties, affects acquisition and maintenance of intravenous heroin self-administration in rats, male Long-Evans rats were trained to press a lever in order to receive heroin (0.05 mg/kg/infusion) under a fixed ratio or a progressive ratio schedule. A control group was trained in a fixed ratio food-reinforced operant procedure. The effect of venlafaxine on operant responding for heroin and food was assessed both during acquisition and, in separate groups of rats, during maintenance (i.e., after acquisition) of self-administration behaviour. Daily treatment with venlafaxine (10 mg/kg i.p.) before the operant session attenuated the acquisition of responding for heroin, but not for food. However, when tested during the maintenance phase in rats showing stable responding, acute treatment with venlafaxine only marginally affected operant responding for heroin under a fixed ratio:10 schedule of reinforcement, and neither acute nor subchronic (once daily during 4 weeks) venlafaxine treatment affected responding under a progressive ratio schedule. Thus, daily treatment with an antidepressant attenuates the acquisition of heroin self-administration in a behaviourally specific manner, while having only marginal effects on maintenance of heroin self-administration.
authors.affiliation: Department of Pharmacology, Preclinical Research and Development, Grünenthal GmbH, 52099 Aachen, Germany.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Magalas
authors.forename: Jean
authors.initials: J
authors.lastname: De Vry
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Tzschentke
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D003511:Cyclohexanols / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D003932:Heroin; D006556:Heroin Dependence / Q000188:drug therapy*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012646:Self Administration; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015819:Substance Abuse, Intravenous / Q000188:drug therapy*; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D003932:Heroin; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride