Incentive salience is a form of attraction to reward associated stimuli, and disrupted incentive salience processing is involved in impulsive choices and vulnerability to addiction. Sign-tracking (ST) phenotype is considered expression of aberrant incentive salience, and dependent on DA transmission within the limbic striatum (Nucleus Accumbens, NAC). We recently found expression of ST in DBA/2J mice (DBA) characterized by genetic reduction of brain serotonin (5-HT) availability and in adult C57BL/6 mice (C57) following a depletion of 5-HT in the medial prefrontal cortex (mPFC). These findings suggest that 5-HT transmission in mPFC is a late developmental stage engaged in inhibitory control of ST behavior likely by inhibiting dopamine (DA) transmission within the NAC. However, DBA and C57 mice are also characterized by genotype-dependent differences in the DA system.
The general aim of the proposed experiment is to test the involvement of DA transmission within the NAC in the expression of ST behavior of young DBA and C57 mice, when mice of both strains express this phenotype. To this aim we will block DA receptors with local infusion of a non-selective antagonist within the NAC after development of ST phenotype.
The experiments proposed aim at identify determinants of neural phenotypic variability in neural mechanisms of "Reward valuation", a functional construct of the "Positive Valence Systems" considered amongst top priorities for research in mental health by both NIH (https://www.nimh.nih.gov/researchpriorities/rdoc/development-and-definit...) and the EC-funded Roadmap for Mental Health Research (ROAMER, 2015). In particular, their results will be most relevant for: " Define the functional characteristics of neurobehavioural mechanisms across the lifespan " one of the 6 research priorities for policy action in mental health and wellbeing research for Europe [1].
[1] Wykes T et al. 2015. Lancet Psychiatry 2:1036-42