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Psychopharmacology (Berl). 2016 Apr;233(7):1157-69. doi: 10.1007/s00213-015-4192-7. Epub 2016 Jan 4.

Role of prefrontal 5-HT in the strain-dependent variation in sign-tracking behavior of C57BL/6 and DBA/2 mice.

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Department of Psychology, University of Rome "Sapienza", Roma, Italy.
Fondazione Santa Lucia IRCSS, European Center for Brain Research, Rome, Italy.
Department of Psychology, University of Rome "Sapienza", Roma, Italy.
Center for Research in Neurobiology "Daniel Bovet", University of Rome "Sapienza", Roma, Italy.
Fondazione Santa Lucia IRCSS, European Center for Brain Research, Rome, Italy.



The expression of sign-tracking (ST) phenotype over goal-tracking (GT) phenotype has been associated to different aspects of impulsive behavior, and depletions of brain serotonin (5-HT) have been shown to selectively increase impulsive action as well as ST.


The present study aimed at testing the relationship between reduced brain 5-HT availability and expression of ST phenotype in a genetic model of individual variation in brain 5-HT functionality. Inbred DBA/2J (DBA) mice are homozygous for the allelic variant of the TPH-2 gene causing lower brain 5-HT function in comparison with C57BL/6J (C57) inbred mice.


Young adult (10 weeks) and adult (14 weeks) C57 and DBA mice were trained in a Pavlovian conditioned approach (PCA) paradigm. Lever-directed (ST) and magazine-directed (GT) responses were measured in 12 daily conditioning sessions. In a second experiment, effect of the medial prefrontal cortex (mPFC) 5-HT depletion by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) was assessed on acquisition of ST phenotype in adult C57 mice, according to their higher 5-HT functionality compared to DBA mice.


Young adult mice of both strains developed ST phenotype, but only adult DBA mice developed ST phenotype. 5-HT depletion in the mPFC of adult C57 mice completely changed their phenotype, as shown by their increased ST.


These findings indicate that ST phenotype can be the expression of a transitory late developmental stage and that genetic factors determine persistence of this phenotype in adulthood. These findings also support a role of 5-HT transmission in PFC in constraining development of ST phenotype.


Autoshaping; Development; Goal tracking; Inbred strain; Individual differences; Pavlovian approach; Serotonin; Sign tracking

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