Psychopharmacology

, Volume 215, Issue 4, pp 631–642

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

  • Price E. Dickson
  • Tiffany D. Rogers
  • Deranda B. Lester
  • Mellessa M. Miller
  • Shannon G. Matta
  • Elissa J. Chesler
  • Dan Goldowitz
  • Charles D. Blaha
  • Guy Mittleman
Original Investigation

DOI: 10.1007/s00213-010-2159-2

Cite this article as:
Dickson, P.E., Rogers, T.D., Lester, D.B. et al. Psychopharmacology (2011) 215: 631. doi:10.1007/s00213-010-2159-2

Abstract

Rationale

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.

Objectives

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.

Keywords

NicotineDopamineBXDC57BL/6JDBA/2JMinipumpElectrochemistryAmperometryBody weightCocaine

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Price E. Dickson
    • 1
  • Tiffany D. Rogers
    • 1
  • Deranda B. Lester
    • 1
  • Mellessa M. Miller
    • 1
  • Shannon G. Matta
    • 2
  • Elissa J. Chesler
    • 3
  • Dan Goldowitz
    • 4
  • Charles D. Blaha
    • 1
  • Guy Mittleman
    • 1
  1. 1.Department of PsychologyUniversity of MemphisMemphisUSA
  2. 2.Department of Anatomy and NeurobiologyUniversity of Tennessee Health Science CenterMemphisUSA
  3. 3.The Jackson LaboratoryBar HarborUSA
  4. 4.Centre for Molecular Medicine and Therapeutics, Department of Medical GeneticsUniversity of British ColumbiaVancouverCanada