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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.

Author information

1
Department of Psychology, University of Rome "Sapienza", Roma, Italy.
2
Fondazione Santa Lucia IRCSS, European Center for Brain Research, Rome, Italy.
3
Department of Psychology, University of Rome "Sapienza", Roma, Italy. cristina.orsini@uniroma1.it.
4
Center for Research in Neurobiology "Daniel Bovet", University of Rome "Sapienza", Roma, Italy. cristina.orsini@uniroma1.it.
5
Fondazione Santa Lucia IRCSS, European Center for Brain Research, Rome, Italy. cristina.orsini@uniroma1.it.

Abstract

RATIONALE:

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.

OBJECTIVES:

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.

MATERIALS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

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

PMID:
26728892
DOI:
10.1007/s00213-015-4192-7
[Indexed for MEDLINE]

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