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Background <p>Inbred mouse strains provide valuable genomic tools to investigate substances of abuse, including nicotine, and the individual vulnerability of smoking-related behaviors. This study was designed to explore diverse genetic influences in nicotine-mediated reward.</p> Methods <p>Potency (ED<sub>50</sub> values) and genetic correlations for nicotine conditioned place preference (CPP) were calculated. We examined multiple doses of nicotine (0.1 to 1.5&#xa0;mg/kg; s.c.) in seven strains of inbred male mice; CBA/J, 129/SvEv, DBA/2J, BALB/cByJ, A/J, C3H/HeJ, and C57BL/6J and three first filial generation (F1) hybrid mice; B6CBAF1, B6129F1 and B6D2F1. A cohort group from each mouse strain was exposed to saline alone.</p> Results <p>Nicotine induced CPP in most strains with an inverted U-shape dose-response curve. However, DBA/2J, and B6D2F1 did not show preference in any dose tested. Separately, CBA/J, DBA/2J, and B6D2F1 all formed an aversion at the highest dose of nicotine tested. The rank order for sensitivity to nicotine-induced CPP was A/J = 129/SvEv &gt; B6129F1 &gt; B6CBAF1 = C57BL/6J &gt; C3H/ HeJ &gt; BALB/ByJ &gt; CBA/J &gt; DBA/2J = B6D2F1. For the 0.25 and 0.5&#xa0;mg/kg nicotine doses, there was a strong pattern of genetic heritability. Across 6 inbred strains, there was a significant, positive correlation between ED<sub>50</sub> values for both nociceptive assays and CPP.</p> Conclusion <p>Overall, genotypes had marked effects on both CPP and antinociception. These data strongly suggest an influence of genetic factors in the rewarding and antinociceptive effects of nicotine, which may influence an individual’s vulnerability to cigarette smoking.</p>

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Nicotine reward in the conditioned place preference test across a panel of male inbred mice and F1 crosses: genetic influence and correlation with variation in nicotine antinociception

  • 期刊论文

  • 发表日期：

    2025年10月15日

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  • Belle Buzzi,
  • Shakir D. AlSharari,
  • Julian Vaughn,
  • Erin Kalck,
  • Walker D. Rogers,
  • Amber Baldwin,
  • Gina M. Fernandez,
  • Michael F. Miles,
  • M. Imad Damaj

摘要

Background

Inbred mouse strains provide valuable genomic tools to investigate substances of abuse, including nicotine, and the individual vulnerability of smoking-related behaviors. This study was designed to explore diverse genetic influences in nicotine-mediated reward.

Methods

Potency (ED50 values) and genetic correlations for nicotine conditioned place preference (CPP) were calculated. We examined multiple doses of nicotine (0.1 to 1.5 mg/kg; s.c.) in seven strains of inbred male mice; CBA/J, 129/SvEv, DBA/2J, BALB/cByJ, A/J, C3H/HeJ, and C57BL/6J and three first filial generation (F1) hybrid mice; B6CBAF1, B6129F1 and B6D2F1. A cohort group from each mouse strain was exposed to saline alone.

Results

Nicotine induced CPP in most strains with an inverted U-shape dose-response curve. However, DBA/2J, and B6D2F1 did not show preference in any dose tested. Separately, CBA/J, DBA/2J, and B6D2F1 all formed an aversion at the highest dose of nicotine tested. The rank order for sensitivity to nicotine-induced CPP was A/J = 129/SvEv > B6129F1 > B6CBAF1 = C57BL/6J > C3H/ HeJ > BALB/ByJ > CBA/J > DBA/2J = B6D2F1. For the 0.25 and 0.5 mg/kg nicotine doses, there was a strong pattern of genetic heritability. Across 6 inbred strains, there was a significant, positive correlation between ED50 values for both nociceptive assays and CPP.

Conclusion

Overall, genotypes had marked effects on both CPP and antinociception. These data strongly suggest an influence of genetic factors in the rewarding and antinociceptive effects of nicotine, which may influence an individual’s vulnerability to cigarette smoking.