title: Stress induces behavioral sensitization, increases nicotine-seeking behavior and leads to a decrease of CREB in the nucleus accumbens.
abstract: Experimental evidence shows that exposure to stress engenders behavioral sensitization and increases drug-seeking and leads to intense drug taking. However the molecular mechanisms involved in these processes is not well known yet. The present experiments examined the effects of exposure to variable stress on nicotine-induced locomotor activation, cAMP-response element-binding protein (CREB) and extracellular signal-regulated kinase (ERK) activity and nicotine intravenous self-administration in rats. Male Wistar rats were exposed to variable stress that consisted of the exposure to different stressors twice a day in random order for 10 days. During this period the control group was left undisturbed except for cage cleaning. Ten days after the last stress episode, rats were challenged with either saline or nicotine (0.4 mg/kgs.c.) and the locomotor activity was recorded for 20 min. Immediately after behavioral recordings rats were sacrificed and their brains were removed to posterior western blotting analysis of CREB, phosphoCREB, ERK and phosphoERK in the nucleus accumbens. An independent set of control and stressed animals were subjected to an intravenous nicotine self-administration protocol. The break point during a progressive ratio schedule and nicotine intake patterns during a 24-hour binge was analyzed. Repeated variable stress caused a sensitized motor response to a single challenge of nicotine and decreased CREB in the nucleus accumbens. Furthermore, in the self-administration experiments previous stress exposure caused an increase in the break point and nicotine intake.
authors.affiliation: Laboratory of Pharmacology, School of Pharmaceutical Sciences, Univ. Estadual Paulista-UNESP, Rod. Araraquara-Jaú Km 1, 14801-902, Araraquara, São Paulo, Brazil.
authors.forename: Rodrigo Molini
authors.initials: RM
authors.lastname: Leão
authors.forename: Fábio Cardoso
authors.initials: FC
authors.lastname: Cruz
authors.forename: Marcelo Tadeu
authors.initials: MT
authors.lastname: Marin
authors.forename: Cleopatra da Silva
authors.initials: Cda S
authors.lastname: Planeta
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D058999:Drug-Seeking Behavior / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013312:Stress, Physiological
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009538:Nicotine; D048049:Extracellular Signal-Regulated MAP Kinases