Aberrations in the elaboration of both aversive and rewarding stimuli characterize
several psychopathologies including anxiety, depression and addiction. Several studies
suggest that different neurotrasmitters, within the corticolimbic system, are critically
involved in the processing of positive and negative stimuli. Individual differences in
this system, depending on genotype, have been shown to act as a liability factor for
different psychopathologies. Inbred mouse strains are commonly used in preclinical
studies of normal and pathological behaviors. In particular, C57BL/6J (C57) and DBA/2J
(DBA) strains have permitted to disclose the impact of different genetic backgrounds
over the corticolimbic system functions. Here, we summarize the main findings
collected over the years in our laboratory, showing how the genetic background
plays a critical role in modulating amminergic and GABAergic neurotransmission in
prefrontal-accumbal-amygdala system response to different rewarding and aversive
experiences, as well as to stress response. Finally, we propose a top-down model for the
response to rewarding and aversive stimuli in which amminergic transmission in prefrontal
cortex (PFC) controls accumbal and amygdala neurotransmitter response