A mouse model of early social interactions after prenatal drug exposure: a genetic investigation

Abstract

The aim of the present study was to (i) characterise the mouse behavioural profile (particularly social interactions) during the preweaning period, (ii) assess the effects of prenatal exposure to an anticonvulsant drug widely used in clinical practice, (iii) examine possible genetic differences both in baseline behavioural profiles and in sensitivity to drug-induced effects. Following a balanced intra-strain fostering procedure, the offspring of C57BL/6J and CBA inbred mouse strains from mothers exposed during pregnancy to either phenobarbitone (PHB, 60 mg/kg) or vehicle (VEH) given intraperitoneally (IP) during days 10-16 of gestation, were observed for early social interactions in the home cage during the last part of the preweaning period (days 20 and 21). The behavioural repertoires of the two strains differed markedly, in that C57 pups were more involved in Play soliciting, Locomotor-rotational play, and in Maintenance activities, while CBA mice spent much more time being inactive or exploring the environment. C57 and CBA mice also differed in the sensitivity to PHB exposure. On the whole, time spent in Investigative/Affiliative behaviours was increased, while the frequency of Play soliciting patterns was reduced in PHB-treated mice. The treatment of the fostering mother had only negligible effects, suggesting that PHB-induced changes in behaviour were largely due to direct effects of the substance on the foetus. These results indicate that specific items of the preweaning behavioural profile, and particularly social interactions, are influenced by early PHB exposure, and that the responses are heavily affected by the genotype.

Behavioral phenotyping of mouse models of neurodevelopmental disorders: Relevant social behavior patterns across the life span

“…However, the intensity of such behavior depends on both sex (females are more affiliative and play for longer), and housing conditions, with social isolation increasing affiliative interactions [153]. The expression of social behavior at this stage has proven to be sensitive to different environmental and pharmacological manipulations [87,151,163]. Social interactions are usually observed in a neutral cage, with clean bedding, and involve sex and age matched individuals.…”

PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain

“…Social approach behaviors become reliably measurable in the mouse around postnatal day 19 (Laviola et al, 1994; Fairless et al, 2012), suggesting PDE11A mutant mice might exhibit social approach deficits early in adolescence. That said, a number of neurodevelopmental insults, including neonatal ventral hippocampal lesions, do not yield immediate behavioral deficits but, rather, require a period of development to occur before deficits fully manifest (e.g., (Tseng et al, 2009)).…”

Sociability and brain development in BALB/cJ and C57BL/6J mice

“…These ages were selected as potentially interesting times for the development of sociability. Mice at 19 days of age are about the youngest mice for which valid data in the Social Approach Test can be obtained, because mice display their first active social interactions around 17 days of age [78,79]. Mice in our colony are weaned near 23 days of age.…”