Affiliation and neophobia in developing mice prenatally exposed to oxazepam

In the framework of the well-known regulatory role of the GABA-benzodiazepine (BZ) mechanisms of the brain in response to social and environmental challenges, we tested the hypothesis that developmental manipulation of this neurochemical system by prenatal BZ exposure can affect the social repertoire and neophobia level in infant mice. Outbred CD-1 mice were treated with either vehicle or oxazepam (15mg/kg p.o. to the dam, twice a day on Days 12-16 of foetal life), and fostered at birth to untreated dams. Two males plus two females were observed in the home cage, in the presence of a novel object, on Postnatal Days 16, 20 and 24. The expression of social and non-social behaviours increased with age. Prenatal oxazepam exposure reduced sex differences by having a more pronounced effect on males than on females; it also produced fairly specific, though subtle, behavioural changes. Oxazepam exposed mice appeared more involved than prenatal controls in behaviours related to the achievement and maintenance of a "passive" proximity with littermates. By contrast, they performed less active investigation and solicitation of littermates, and non-social behaviours such as locomotor-rotational play, cage exploration, and maintenance activities; they also showed a reduced frequency of approaching and making contact with the novel object. Analysis of social interactions of infant mice seems to represent a sensitive tool for early detection of subtle developmental changes in the CNS.