title: Nicotinic cholinergic and dopaminergic receptor mRNA expression in male and female rats with high or low preference for nicotine.
abstract: Nicotine exerts its central actions through nicotinic acetylcholine receptors (nAChRs), which in turn regulate major neurotransmitter systems including dopamine. Nicotinic and dopaminergic systems play significant roles in physiological functions, neuropsychiatric disorders, and addiction.
  
  
  
  To evaluate possible differences in the expression of nAChR subunit and dopamine receptor (DR) mRNAs following voluntary nicotine intake.
  
  
  
  Male and female rats (n = 67) were exposed to long-term free-choice oral nicotine (24 hours/day, 6 weeks); rats with maximum and minimum nicotine preference/intake were selected. The mRNA levels of genes encoding α4,β2,α5, and α7 nAChR subunits and DR Drd1and Drd2 subtypes were evaluated in the striatum (STR), prefrontal cortex (PFC), and hippocampus using quantitative real-time polymerase chain reaction in selected rats (n = 30) and their control groups (n = 15).
  
  
  
  In addition to baseline differences, expression changes were observed in the mRNA levels of evaluated genes in rats exposed to voluntary oral nicotine in a brain region-, sex-, and preference-related manner. Nicotine intake is correlated negatively with Chrnb2, Chrna7 and positively with Drd1 expression. In the cholinergic system, regional differences in Chnrb2 and Chrna5, sex differences in Chrna4 and Chrna5, and nicotine preference effects in the expression of all subunits except α4 were observed. Chrna5 was lower in maximum than in minimum preferring, and in male than female rats, supporting the inhibitory role of the α5 subunit in nicotine dependence. Nicotine increased Drd2 mRNA expression only in minimum preferring female rats in STR and PFC.
  
  
  
  Modulation of nAChR and DR gene expression by nicotine may have clinical implications and aid drug development. Pharmaceuticals targeting the nicotinic cholinergic and dopaminergic systems might be expected to have differential efficacy that varies with the patient's sex or smoking status.
authors.affiliation: a Center for Brain Research , Ege University , Bornova , Izmir , Turkey.|b School of Medicine Department of Physiology , Ege University , Bornova , Izmir , Turkey.
authors.forename: Oguz
authors.initials: O
authors.lastname: Gozen
authors.affiliation: a Center for Brain Research , Ege University , Bornova , Izmir , Turkey.
authors.forename: Tanseli
authors.initials: T
authors.lastname: Nesil
authors.affiliation: a Center for Brain Research , Ege University , Bornova , Izmir , Turkey.|b School of Medicine Department of Physiology , Ege University , Bornova , Izmir , Turkey.
authors.forename: Lutfiye
authors.initials: L
authors.lastname: Kanit
authors.affiliation: a Center for Brain Research , Ege University , Bornova , Izmir , Turkey.|b School of Medicine Department of Physiology , Ege University , Bornova , Izmir , Turkey.
authors.forename: Ersin O
authors.initials: EO
authors.lastname: Koylu
authors.affiliation: a Center for Brain Research , Ege University , Bornova , Izmir , Turkey.
authors.forename: Sakire
authors.initials: S
authors.lastname: Pogun
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000378:metabolism; D021122:Protein Subunits / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012646:Self Administration; D012727:Sex Characteristics
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011978:Receptors, Nicotinic; D009538:Nicotine
keywords: Nicotine; dopamine; dopamine receptor; mRNA; nicotine preference; nicotinic receptor; sex differences