title: Sex differences and repeated intravenous nicotine: behavioral sensitization and dopamine receptors.
abstract: The present study examined the sex-dependent expression of behavioral sensitization as well as changes of dopamine (DA) transporters and D1, D2, and D3 receptors following repeated intravenous nicotine administration. Male and female Sprague-Dawley rats were implanted with indwelling jugular catheters, equipped with subcutaneous intravenous injection ports. Rats were habituated to activity chambers for 3 days and were subsequently administered 15-s bolus injections of intravenous nicotine (50 microg/kg/ml) 1/day for 21 days. Animals were placed in activity chambers for 60 min immediately after the 1st and 21st nicotine injection. Observational time sampling was also performed. Brains were subsequently removed and frozen for autoradiographic DA transporter/DA receptor analysis on the afternoon females were in proestrus. With one exception, no robust sex differences were observed for locomotor activity or any rearing measures either during baseline or after initial nicotine injection. Females exhibited markedly more behavioral sensitization of locomotor activity, rearing, duration of rearing, and incidence of observed rearing. There were no sex differences in the number of D1 or D2 receptors. Females exhibited an increased number of DA transporters and decreased D3 receptors in the NAcc, relative to males. Multiple regression analyses suggest that D3 receptors and DA transporters in various striatal and NAcc subregions differentially predicted nicotine-induced behaviors for males and females. Collectively, these findings demonstrate that repeated intravenous nicotine produces sex differences in the expression of behavioral sensitization, and suggest that nicotine-induced changes of DA transporters and D3 receptors are partly responsible for increased behavioral sensitization in female rats.
authors.affiliation: Department of Psychology, University of South Carolina, 1512 Pendleton Street, Columbia, SC 29208, USA. harrods@gwm.sc.edu
authors.forename: Steven B
authors.initials: SB
authors.lastname: Harrod
authors.forename: Charles F
authors.initials: CF
authors.lastname: Mactutus
authors.forename: Klark
authors.initials: K
authors.lastname: Bennett
authors.forename: Ulla
authors.initials: U
authors.lastname: Hasselrot
authors.forename: Guanghan
authors.initials: G
authors.lastname: Wu
authors.forename: Marion
authors.initials: M
authors.lastname: Welch
authors.forename: Rosemarie M
authors.initials: RM
authors.lastname: Booze
mesh_terms: D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D026901:Membrane Transport Proteins / Q000032:analysis; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000032:analysis*; D017447:Receptors, Dopamine D1 / Q000032:analysis; D017448:Receptors, Dopamine D2 / Q000032:analysis; D050637:Receptors, Dopamine D3; D012044:Regression Analysis; D012727:Sex Characteristics
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493595:Drd3 protein, rat; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D009538:Nicotine