title: Enhanced nicotine-seeking behavior following pre-exposure to repeated cocaine is accompanied by changes in BDNF in the nucleus accumbens of rats.
abstract: We investigated the behavioral and molecular interactions between cocaine and nicotine, through evaluating locomotor activity, nicotine intravenous self-administration and gene expression. Locomotor sensitization was induced in male Wistar rats by repeated cocaine (20 mg/kg; i.p.) or saline injections once a day over 7 days. Three days after the last injection, rats were challenged with either saline or cocaine (15 mg/kg; i.p.) and the locomotor activity was measured. The very next day animals received either saline or nicotine (0.4 mg/kg; s.c.) and the locomotor cross-sensitization was tested. Animals were then prepared with intrajugular catheters for nicotine self-administration. Nicotine self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement and a 24-h unlimited access binge. Immediately after the binge sessions animals were decapitated, the brains were removed and the nucleus accumbens was dissected. The dynorphin (DYN), μ-opioid receptor (mu opioid), neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), tropomyosin-related tyrosine kinase B receptor (TrkB) and corticotropin-releasing factor receptor type 1 (CRF-R1) gene expression were measured by the reverse transcription-polymerase chain reaction (RT-PCR). Pretreatment with cocaine caused sensitization of cocaine motor response and locomotor cross-sensitization with nicotine. In the self-administration experiments repeated cocaine administration caused an increase in the nicotine break point and nicotine intake during a 24 h binge session.
authors: Laboratory of Pharmacology, School of Pharmaceutical Sciences, Univ. Estadual Paulista UNESP, Rod. Araraquara-Jaú Km 1, 14801-902, Araraquara, São Paulo, Brazil.
authors: Rodrigo M
authors: RM
authors: Leão
authors: Fábio C
authors: FC
authors: Cruz
authors: Paulo E
authors: PE
authors: Carneiro-de-Oliveira
authors: Daniella B
authors: DB
authors: Rossetto
authors: Sandro R
authors: SR
authors: Valentini
authors: Cleslei F
authors: CF
authors: Zanelli
authors: Cleopatra S
authors: CS
authors: Planeta
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003042:Cocaine / Q000008:administration & dosage*; D004399:Dynorphins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009478:Neuropeptide Y / Q000235:genetics; D009538:Nicotine / Q000008:administration & dosage; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D012307:Risk Factors; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D000099052:CRF Receptor, Type 1
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009478:Neuropeptide Y; D018019:Receptors, Corticotropin-Releasing Hormone; D017450:Receptors, Opioid, mu; D000099052:CRF Receptor, Type 1; D009538:Nicotine; D004399:Dynorphins; D020813:Receptor, trkB; D003042:Cocaine