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

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.

Positive emotional arousal increases duration of memory traces: different role of dopamine D1 receptor and ß-adrenoceptor activation.

We investigated the effects of post-training administration of dopamine D1 receptor antagonist SCH 23390 and ß-adrenergic receptor antagonist Propranolol on memory retention of an object sampled in a state of positive emotional arousal. Saline-treated mice trained and tested under high emotional/motivational arousal (High) showed discrimination of a novel object both 24 and 96 h post-training. Instead, mice trained and tested under low motivational arousal (Low) were unable to discriminate the novel object 96 h post-training. Both a high (2 mg/kg) and a low (1 mg/kg) dose of Propranolol reduced object discrimination in High mice tested 24 h post-training, whereas neither dose was effective in Low mice. A high dose of SCH 23390 (0.025 mg/kg) reduced discrimination of the novel object in High mice tested both 24 and 96 h post-training, whereas a low dose of the D1 antagonist (0.01 mg/kg) reduced discrimination in High mice tested 96 h post-training and abolished discrimination in Low mice tested 24h after training.