title: Olfactory bulbectomy increases reinstatement of methamphetamine seeking after a forced abstinence in rats.
abstract: Drug addiction is commonly associated with depression and comorbid patients also suffer from higher cravings and increased relapse rate. To address this issue preclinically we combined the olfactory bulbectomy (OBX) model of depression and intravenous methamphetamine self-administration procedure in rats to assess differences in relapse-like behavior. Male Sprague-Dawley rats were divided randomly into two groups; in one group the bilateral olfactory bulbectomy (OBX) was performed while the other group was sham operated. After recovery, intracardiac catheter was implanted. Intravenous self-administration procedure was conducted in operant boxes using nose-poke operandi (Coulbourn Instruments, Inc., USA) under fixed ratio 1 schedule of reinforcement. Methamphetamine was available at dose 0.08 mg/kg/infusion. After stable methamphetamine intake was maintained, a period of forced abstinence was initiated and rats were kept in their home-cages for 14 days. Finally, one reinstatement session was conducted in operant boxes with no drug delivery. In the reinstatement session the mean of 138.4 active nose-pokes was performed by the OBX group, while the sham group displayed 41 responses, i.e. 140 % and 48 % of basal nose-poking during maintenance phase in OBX and sham operated group respectively. OBX group also showed significantly more passive nose-pokes indicating hyperactive behavioral traits in bulbectomized rats. However, the % of active operandum preference was equal in both groups. Olfactory bulbectomy model significantly increased reinstatement of methamphetamine seeking behavior. This paradigm can be used to evaluate potential drugs that are able to suppress the drug-seeking behavior.
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic; Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Babinska
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic; Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Ruda-Kucerova
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic; Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Amchova
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Merhautova
authors.affiliation: Masaryk University, Institute of Biostatistics and Analyses of Faculty of Medicine, Kamenice 3, 625 00 Brno, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Dusek
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic. Electronic address: jkucer@med.muni.cz.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sulcova
mesh_terms: D061605:Administration, Intravenous; D019969:Amphetamine-Related Disorders / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D002408:Catheters, Indwelling; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003866:Depressive Disorder / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior / Q000502:physiology*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D009830:Olfactory Bulb / Q000503:physiopathology* / Q000601:surgery; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012646:Self Administration
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine
keywords: Sprague-Dawley rats; depression; methamphetamine; olfactory bulbectomy; reinstatement; self-administration