• C57Bl/6J;
  • CD-1;
  • Adenosine;
  • Saccharin;
  • Caffeine;
  • In Situ Hybridization Histochemistry;
  • In Vitro Autoradiography

Background: To extend the known phenotype of strains commonly used in the development of mutant mice, ethanol, saccharin, and caffeine preferences were examined in C57Bl/6J, CD-1, and hybrid C57Bl/6J × CD-1 mice. As dopaminergic mechanisms are inherently involved in the neuronal processing of many drugs of abuse (including ethanol), and an important role for adenosine–dopamine interactions has also been reported, the dopaminergic and purinergic neurochemical profiles of mice were compared against the consummatory phenotype observed.

Methods: Ethanol (5% v/v), saccharin (0.1% w/v), and caffeine (0.1% w/v) consumption and preference were examined using a 2-bottle free-choice paradigm. Dopamine and adenosine receptor and transporter mRNA and protein density were quantified using in situ hybridization histochemistry and in vitro autoradiography, respectively.

Results: C57Bl/6J and hybrid C57Bl/6J × CD-1 mice demonstrated a clear ethanol preference, voluntarily consuming large quantities of ethanol when given the choice between drinking vessels containing either ethanol or water. Conversely, CD-1 mice were characterized as ethanol-avoiding under the present paradigm. Differences in D1 receptor mRNA between the strains were consistent with the observed behavioral differences in ethanol preference. The high ethanol-preferring phenotype of C57Bl/6J mice could not be directly linked to alterations in dopamine transporter neurochemistry and/or enkephalin levels as proposed by earlier researchers. Ethanol-seeking behavior appeared to correlate with D2 receptor expression, however, with evidence that ethanol-preferring mice also exhibit an increased density of D2 receptors within limbic dopaminergic projection nuclei. Interestingly, strain differences in the expression of the ethanol-sensitive nucleoside transporter paralleled differences in ethanol consumption, a novel finding consonant with purinergic involvement in dopamine-related behaviors.

Conclusions: This study has highlighted the relevance of alterations in dopamine receptor expression and purinergic modulation within the mesolimbic pathway and predisposition toward the development of ethanol-seeking behavior.