title: N-acetylcysteine attenuates nicotine-induced kindling in female periadolescent rats.
abstract: Kindling is a form of behavioral sensitization that is related to the progression of several neuropsychiatric disorders such as bipolar disorder. We recently demonstrated that female periadolescent rats are more vulnerable to nicotine (NIC)-induced kindling than their male counterparts. Furthermore, we evidenced that decreases in brain antioxidative defenses may contribute to this gender difference. Here we aimed to determine the preventive effects of the antioxidant N-acetyl cysteine (NAC) against NIC-kindling in female periadolescent rats. To do this female Wistar rats at postnatal day 30 received repeated injections of NIC 2mg/kg, i.p. every weekday for up to 19 days. NAC90, 180 or 270 mg/kg, i.p. was administered 30 min before NIC. The levels of glutathione (GSH), superoxide dismutase (SOD) activity, lipid peroxidation (LP) and nitrite were determined in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The development of kindling occurred at a median time of 16.5 days with 87.5% of NIC animals presenting stage 5 seizures in the last day of drug administration. NAC270 prevented the occurrence of kindling. NIC-kindled animals presented decreased levels of GSH and increased LP in the PFC, HC and ST, while SOD activity was decreased in the ST. NAC180 or 270 prevented the alterations in GSH induced by NIC, but only NAC270 prevented the alterations in LP. Nitrite levels increased in the ST of NAC270 pretreated NIC-kindled animals. Taken together we demonstrated that NAC presents anti-kindling effects in female animals partially through the restoration of oxidative alterations.
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Adriana Mary Nunes Costa
authors.initials: AM
authors.lastname: Okamura
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Patrícia Xavier L
authors.initials: PX
authors.lastname: Gomes
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Gersilene V
authors.initials: GV
authors.lastname: de Oliveira
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Fernanda Yvelize R
authors.initials: FY
authors.lastname: de Araújo
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Viviane S
authors.initials: VS
authors.lastname: Tomaz
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Adriano José Maia
authors.initials: AJ
authors.lastname: Chaves Filho
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Francisca Cléa F
authors.initials: FC
authors.lastname: de Sousa
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Silvânia Maria Mendes
authors.initials: SM
authors.lastname: Vasconcelos
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: David Freitas
authors.initials: DF
authors.lastname: de Lucena
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address: daniellesilmacedo@gmail.com.
authors.forename: Danielle
authors.initials: D
authors.lastname: Macêdo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000097:blood; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D018722:Nicotinic Agonists; D009573:Nitrites; D004958:Estradiol; D009538:Nicotine; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine
keywords: Female rats; Kindling; N-acetyl cysteine; Nicotine; Nicotine kindling; Seizure