title: Effects of combined nicotine and fluoxetine treatment on adult hippocampal neurogenesis and conditioned place preference.
abstract: Adult neurogenesis occurs in mammals within the dentate gyrus, a hippocampal subarea. It is known to be induced by antidepressant treatment and reduced in response to nicotine administration. We checked here whether the antidepressant fluoxetine would inverse the decrease in hippocampal neurogenesis caused by nicotine. It is shown that repeated, but not a single injection of rats with fluoxetine was able to abolish the decrease in adult dentate cell proliferation produced by nicotine treatment. We measured the expression of several biochemical parameters known to be associated with neurogenesis in the dentate gyrus. Both drugs increased the expression of p75 neurotrophin receptor, which promotes proliferation and early maturation of dentate gyrus cells. Using the conditioned place preference (CPP) paradigm, we also gave both drugs in a context in which their rewarding properties could be measured. Fluoxetine produced a significant but less robust CPP than nicotine. A single injection of fluoxetine was found to reduce nicotine-induced CPP. Moreover, the rewarding properties of nicotine were completely abolished in response to repeated fluoxetine injections. Expression of nicotine-induced CPP was accompanied by an increase of phospho-CREB (cyclic AMP-responsive element-binding protein) and HDAC2 (histone deacetylase 2) expression in the nucleus accumbens. The data suggest that fluoxetine reward, as opposed to nicotine reward, depends on dentate gyrus neurogenesis. Since fluoxetine was able to disrupt the association between nicotine and the environment, this antidepressant may be tested as a treatment for nicotine addiction using cue exposure therapy.
authors.affiliation: Departmento de Fisiología e Instituto de Fisiología y Biofísica (IFIBIO-Houssay), Universidad de Buenos Aires, Paraguay 2155, Buenos Aires C1121ABG, Argentina. Electronic address: pfaillace@qb.ffyb.uba.ar.
authors.forename: M P
authors.initials: MP
authors.lastname: Faillace
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, 12 rue Goethe, Strasbourg, France. Electronic address: zwiller@unistra.fr.
authors.forename: J
authors.initials: J
authors.lastname: Zwiller
authors.affiliation: Departmento de Fisiología e Instituto de Fisiología y Biofísica (IFIBIO-Houssay), Universidad de Buenos Aires, Paraguay 2155, Buenos Aires C1121ABG, Argentina. Electronic address: rbernabeu@fmed.uba.ar.
authors.forename: R O
authors.initials: RO
authors.lastname: Bernabeu
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology*; D056464:Histone Deacetylase 2 / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012201:Reward; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
chemical_list: D005473:Fluoxetine; D056464:Histone Deacetylase 2; D009419:Nerve Tissue Proteins; D009538:Nicotine; D018722:Nicotinic Agonists; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D017367:Selective Serotonin Reuptake Inhibitors; C068313:Ngfr protein, rat; C533426:Hdac2 protein, rat
keywords: conditioned place preference; fluoxetine; histone deacetylase; neurogenesis; nicotine; phospho-CREB