title: Genotype-dependent effects of adolescent nicotine exposure on dopamine functional dynamics in the nucleus accumbens shell in male and female mice: a potential mechanism underlying the gateway effect of nicotine.
abstract: BACKGROUND
  The tendency to use cocaine is determined by genetic and environmental effects across the lifespan. One critical environmental effect is early drug exposure, which is both driven by and interacts with genetic background. The mesoaccumbens dopamine system, which is critically involved in the rewarding properties of drugs of abuse, undergoes significant development during adolescence, and thus may be at particular risk to repeated nicotine exposure during this period, thereby establishing vulnerability for subsequent adult psychostimulant use.
  
  
  OBJECTIVE
  We tested the hypotheses that adolescent nicotine exposure results in attenuation of the enhancing effects of cocaine on medial forebrain bundle (MFB) electrical stimulation-evoked dopamine release in the nucleus accumbens shell (AcbSh) in adulthood and that this effect is significantly influenced by genotype.
  
  
  METHODS
  Mice from the progenitor strains C57BL/6J and DBA/2J and those from the BXD20/TyJ and BXD86/RwwJ recombinant inbred lines were exposed to nicotine via osmotic minipumps from postnatal day (P) 28 to P56. When mice reached P70, dopamine functional dynamics in AcbSh was evaluated by means of in vivo fixed potential amperometry in combination with electrical stimulation of mesoaccumbens dopaminergic axons in the MFB.
  
  
  RESULTS
  Adolescent exposure to nicotine in all strains dose-dependently reduced the ability of a fixed-dose challenge injection of cocaine (10 mg/kg, i.p.) to enhance MFB electrical stimulation-evoked dopamine release in AcbSh in adults. The magnitude of this effect was genotype-dependent.
  
  
  CONCLUSIONS
  These results suggest a genotype-dependent mechanism by which nicotine exposure during adolescence causes persistent changes in the sensitivity to "hard" stimulants such as cocaine.
authors.affiliation: Department of Psychology, University of Memphis, Memphis, TN 38152, USA.
authors.forename: Price E
authors.initials: PE
authors.lastname: Dickson
authors.forename: Tiffany D
authors.initials: TD
authors.lastname: Rogers
authors.forename: Deranda B
authors.initials: DB
authors.lastname: Lester
authors.forename: Mellessa M
authors.initials: MM
authors.lastname: Miller
authors.forename: Shannon G
authors.initials: SG
authors.lastname: Matta
authors.forename: Elissa J
authors.initials: EJ
authors.lastname: Chesler
authors.forename: Dan
authors.initials: D
authors.lastname: Goldowitz
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blaha
authors.forename: Guy
authors.initials: G
authors.lastname: Mittleman
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D012201:Reward; D012727:Sex Characteristics; D013045:Species Specificity
chemical_list: D009538:Nicotine; D003042:Cocaine; D004298:Dopamine