Tph2 deficiency leads to alterations in social adjustment and socio-affective communication in neonatal rats: No rescue effect of communal nesting
Year: 2025
Type: article
Abstract: Deficiency of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme for serotonin (5-hydroxytryptamine, 5-HT) synthesis in the brain, was repeatedly reported to cause impairments in socio-affective communication and maternal affiliation across species, including mice, rats, and monkeys. We recently applied a rescue protocol in the Tph2 knockout rat model and demonstrated that communal nesting ameliorates maternal affiliation impairments. Interestingly, however, this rescue strategy did not lead to improvements in socio-affective communication and was associated with an aggravated growth retardation phenotype in Tph2 -deficient offspring. In the present study, we aimed to gain deeper insight into the interplay between socio-affective communication, nesting condition, and test context. To this aim, we studied Tph2 −/− knockout, Tph2 +/− heterozygous, and Tph2 +/+ wildtype rat pups of both sexes, randomly assigned to standard versus communal nesting. We performed detailed spectrographic analyses and compared the emission of isolation-induced ultrasonic vocalizations under social test conditions, i.e., the maternal preference test and the homing test, to non-social test conditions, i.e., the isolation box test. Our results show that Tph2 deficiency causes prominent alterations in isolation-induced ultrasonic calling linked to reduced maternal responsiveness, including changes in acoustic features, e.g., increased call duration but reduced frequency modulation. Remarkably, irrespective of communal nesting, Tph2 −/− pups typically displayed either no evidence for social adjustment or even changes opposite to Tph2 +/+ littermates, suggesting a reduction and/or delay in the capability and/or motivation to appropriately adjust to changes in the social environment. Such alterations in social adjustment likely contribute to growth retardation through reduced quality of mother-pup interactions. • Tph2 deficiency causes prominent alterations in isolation-induced ultrasonic calling in rat pups. • Tph2 deficiency leads to a reduction and/or delay in the capability and/or motivation to adjust to the social environment. • Communal nesting does not rescue the deficits in socio-affective communication driven by Tph2 deficiency.
Institutions: Philipps University of Marburg, Radboud University Nijmegen, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Neuroscience, Max Delbrück Center, German Centre for Cardiovascular Research, Charité - Universitätsmedizin Berlin, University of Lübeck, Icahn School of Medicine at Mount Sinai, KU Leuven
Language: English
Subfield: Social Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $4,380
Awards: G1794196980, TRR 289: Der Einfluss von Erwartung auf die Wirksamkeit medizinischer Behandlungen, G2634894144, SoundsGood! – An integrated platform for studying ultrasonic vocalizations in rodent models for brain disorders., G4047216823, G434337789, Serotonin and BEYOND: Brain development research Excelling Young Ones in Neurotechnologies and Discoveries, GRK 2271: Beibehaltung vs. Veränderung von Erwartungen im Kontext von Erwartungsverletzungen: Eine Verknüpfung verschiedener Ansätze, Deciphering socio-affective communication through ultrasonic vocalizations in rodents: Improving translational research models for neuropsychiatric dysfunctions., G7651221496, G788223370, SoundsGood! – An integrated platform for studying ultrasonic vocalizations in rodent models for brain disorders., Serotonin and BEYOND: Brain development research Excelling Young Ones in Neurotechnologies and Discoveries
OpenAlex ID: W4413138760