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.
Document Type
Article
Publication Date
2011
Keywords
Animals, Cocaine, Cocaine-Related-Disorders, Dopamine, Genotype, Mice-Inbred-C57BL, Mice-Inbred-DBA, Nicotine, Nucleus-Accumbens, Reward, Sex-Characteristics, Species-Specificity
JAX Location
see Reprint Collection (a pdf is available)
JAX Source
Psychopharmacology (Berl) 2011 Jun; 215(4):631-42.
First Page
631
Last Page
642
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.
Recommended Citation
Dickson PE,
Rogers TD,
Lester DB,
Miller MM,
Matta SG,
Chesler EJ,
Goldowitz D,
Blaha CD,
Mittleman G.
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. Psychopharmacology (Berl) 2011 Jun; 215(4):631-42.