title: Striatal NOS1 has dimorphic expression and activity under stress and nicotine sensitization.
abstract: Nicotine exerts its addictive influence through the meso-cortico-limbic reward system, where the striatum is essential. Nicotine addiction involves different neurotransmitters, nitric oxide (NO) being especially important, since it triggers the release of the others by positive feedback. In the nervous system, NO is mainly produced by nitric oxide synthase 1 (NOS1). However, other subtypes of synthases can also synthesize NO, and little is known about the specific role of each isoform in the process of addiction. In parallel, NOS activity and nicotine addiction are also affected by stress and sexual dimorphism. To determine the specific role of this enzyme, we analyzed both NOS expression and NO synthesis in the striatum of wild-type and NOS1-knocked out (KO) mice of both sexes in situations of nicotine sensitization and stress. Our results demonstrated differences between the caudate-putamen (CP) and nucleus accumbens (NA). With respect to NOS1 expression, the CP is a dimorphic region (27.5% lower cell density in males), but with a stable production of NO, exclusively due to this isoform. Thus, the nitrergic system of CP may not be involved in stress or nicotine addiction. Conversely, the NA is much more variable and strongly involved in both situations: its NO synthesis displays dimorphic variations at both basal (68.5% reduction in females) and stress levels (65.9% reduction in males), which disappear when nicotine is infused. Thus, the KO animals showed an increase in NO production (21.7%) in the NA, probably by NOS3, in an attempt to compensate the lack of NOS1.
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain; Institute of Biomedical Research of Salamanca, IBSAL, Salamanca, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Díaz
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain.
authors.forename: Azucena Rodrigo
authors.initials: AR
authors.lastname: Murias
authors.affiliation: Applied Statistics Group, Department of Statistics, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Carmelo Antonio
authors.initials: CA
authors.lastname: Ávila-Zarza
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain; Institute of Biomedical Research of Salamanca, IBSAL, Salamanca, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Muñoz-Castañeda
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain; Institute of Biomedical Research of Salamanca, IBSAL, Salamanca, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Aijón
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain; Institute of Biomedical Research of Salamanca, IBSAL, Salamanca, Spain; Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Alonso
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain; Institute of Biomedical Research of Salamanca, IBSAL, Salamanca, Spain. Electronic address: ewp@usal.es.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Weruaga
mesh_terms: D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000201:enzymology*; D004195:Disease Models, Animal; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology*; D011699:Putamen / Q000187:drug effects / Q000201:enzymology*; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000201:enzymology*; D014029:Tobacco Use Disorder / Q000201:enzymology*
chemical_list: D007527:Isoenzymes; D018722:Nicotinic Agonists; D009569:Nitric Oxide; D009538:Nicotine; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse
keywords: Caudate-putamen; Nicotine; Nitric oxide synthase; Nucleus accumbens; Striatum