Acute dietary tryptophan manipulation differentially alters social behavior, brain serotonin and plasma corticosterone in three inbred mouse strains. (March 2015)

• Record Type: Journal Article
• Authors: Zhang, Wynne Q.; Smolik, Corey M.; Barba-Escobedo, Priscilla A.; Gamez, Monica; Sanchez, Jesus J.; Javors, Martin A.; Daws, Lynette C.; Gould, Georgianna G.
• Is Part Of: Neuropharmacology. Volume 90(2015)
• Page Start: 1
• Page End: 8
• Publication Date: 2015-03
• Subjects: 129S1/SvImJ -- Autism -- BTBR -- C57BL/6 -- Grooming -- Marble burying -- Serotonin -- Social behavior -- Tryptophan; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2014.10.024
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Clinical evidence indicates brain serotonin (5-HT) stores and neurotransmission may be inadequate in subpopulations of individuals with autism, and this may contribute to characteristically impaired social behaviors. Findings that depletion of the 5-HT precursor tryptophan (TRP) worsens autism symptoms support this hypothesis. Yet dietetic studies show and parents report that many children with autism consume less TRP than peers. To measure the impact of dietary TRP content on social behavior, we administered either diets devoid of TRP, with standard TRP (0.2 g%), or with 1% added TRP (1.2 g%) overnight to three mouse strains. Of these, BTBRT + Itpr3 tf /J and 129S1/SvImJ consistently exhibit low preference for social interaction relative to C57BL/6. We found that TRP depletion reduced C57BL/6 and 129S social interaction preference, while TRP enhancement improved BTBR sociability ( p < 0.05; N = 8–10). Subsequent marble burying did not differ among diets or strains. After behavior tests, brain TRP levels and plasma corticosterone were higher in TRP enhanced C57BL/6 and BTBR, while 5-HT levels were reduced in all strains by TRP depletion ( p < 0.05; N = 4–10). Relative hyperactivity of BTBR and hypoactivity of 129S, evident in self-grooming and chamber entries during sociability tests, were uninfluenced by dietary TRP. Our findings demonstrate mouse sociability and brain 5-HT turnover are reduced by acute TRP depletion, and can be enhanced by TRP supplementation. This outcome warrants further basic and clinical studies employing biomarker combinations such as TRP metabolism and 5-HT regulated hormones to characterize conditions wherein TRP supplementation may best ameliorate sociability deficits. Highlights: Acute dietary tryptophan (TRP) effects on social behavior were studied. Mouse strains used were BTBR T + Itpr3 tf /J, 129S1/SvImJ and C57BL/6J. TRP depletion impaired sociability in two strains and reduced brain 5-HT. TRP enhancement improved sociability in BTBR mice. Serum corticosterone was increased by sociability testing.