title: The effects of N-acetylcysteine on cocaine reward and seeking behaviors in a rat model of depression.
abstract: Depression and substance-abuse (e.g., cocaine) disorders are common concurrent diagnoses. In the present study, we combined bilateral olfactory bulbectomy (OBX) with a variety of procedures of intravenous cocaine self-administration and extinction/reinstatement in rats. We also investigated the effects of N-acetylcysteine (NAC) on rewarding and seeking behaviors for cocaine in OBX rats and compared the drug's effects in sham-operated control animals (SHAM). The occurrence of depressive symptoms before introduction to cocaine self-administration enhanced subsequent cocaine-seeking behaviors but did not significantly influence cocaine's rewarding properties or extinction training. NAC (25-100mg/kg) given acutely or repeatedly did not alter the co-occurrence of cocaine reward and depression but effectively reduced the cocaine-seeking behavior observed in both phenotypes. Our results indicate that depression behavior is linked to more pronounced drug craving and a higher propensity to relapse in rats. We also show the lack of efficacy of repeated NAC treatment on SHAM or OBX animals in terms of cocaine self-administration, while the drug was an effective blocker of cocaine-seeking behavior in both studied phenotypes, with a more pronounced drug effect observed in OBX animals. The last finding demonstrates the potential clinical utility of NAC to reduce cocaine seeking enhanced by co-existing depression.
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland. Electronic address: frankow@if-pan.krakow.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Frankowska
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jastrzębska
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Nowak
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Białko
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Przegaliński
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland; Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Kraków, Medyczna 9, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009830:Olfactory Bulb / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D016166:Free Radical Scavengers; D003042:Cocaine; D000111:Acetylcysteine
keywords: Bulbectomy; Cocaine; Depression; N-acetylcysteine; Seeking-behavior; Self-administration