Abstract
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.
Highlights
Adaptive behavior involves the ability to represent the value of positive or negative stimuli, establish predictions about them, and use these predictions to guide behavior (O’Doherty, 2004)
This study showed that exposure to a novel stressor promotes a rapid, massive, and transient increase in NE release in the medial prefrontal cortex (mpFC), paralleling the rise in mesoaccumbens DA release (Pascucci et al, 2007)
We have demonstrated that a stressful experience, such as restraint, increases 5-HT levels in the mpFC and GABA levels in the amygdala and that selective depletion of cortical 5-HT canceled out these stress-induced responses, implicating prefrontal 5-HT in the control of GABAergic transmission in the amygdala during stress exposure
Summary
Adaptive behavior involves the ability to represent the value of positive or negative stimuli, establish predictions about them, and use these predictions to guide behavior (O’Doherty, 2004). The main findings collected over the years in our lab, by microdialysis experiments, have identified the role of several prefrontal cortex-accumbal-amygdala neurotransmitter systems in the elaboration of rewarding or aversive stimuli.
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