Different dopaminergic mechanism in the expression of sign-tracking phenotype in C57BL/6J and DBA/2J mice

Aims: Sign-tracking (ST) behavior is a phenotype characterized by attraction to a reward-associated stimulus due to incentive salience attribution and it’s considered an endophenotype of vulnerability to drug addiction. Such phenotype is dependent on Dopamine (DA) transmission within the Nucleus Accumbens core (NACc), as DA suppression prevents both its development and expression. However, previous studies suggested the hypothesis that ST behavior can be dependent on different neural mechanisms in two inbred strains of C57BL/6J (C57) and DBA/2J (DBA) mice, which have known differences in their meso-cortico-limbic DA function. Thus, the present study aimed to investigate the role of DA in the expression of ST phenotype in these two inbred strains of mice. Methods: After ST development, C57 and DBA mice were infused within the NACc with the mixed D1/D2 antagonist flupentixol (Exp. 1) or the selective D1 and D2 antagonists SCH23390 and sulpiride (Exp. 2) 10 minutes before the regular PCA training session. Finally, the expression of Drd2 gene mRNA positive neurons (DRD+) within the NACc was investigated by an in situ hybridization. Results: ST behavior of C57 mice was dose-dependently decreased by the mixed D1/D2 receptor antagonism, while only the selective D2 receptor antagonism reduced ST behavior in DBA mice, thus evidencing different DAergic mechanism underlying ST phenotype in these strains. Conclusion: Knowledge of the different neural mechanism underlying similar phenotypes responds to the call for searching the link between individual differences and different trajectories to psychopathology, according to the Precision Psychiatry approach.