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Sexual segregation in infant mice: behavioural and neuroendocrine responses to d-amphetamine administration
F Cirulli1, W Adriani, G Laviola
1Section of Behavioural Pathophysiology, Istituto Superiore di Sanità, Roma, Italy.
Insights
Early life social environment and maternal deprivation significantly impact neuroendocrine and behavioral responses to amphetamine in mice. These factors can alter stress reactivity and monoaminergic system function, influencing individual differences.
Area of Science:
- Neuroscience
- Developmental Psychology
- Endocrinology
Background:
- Individual differences in behavior and neuroendocrine function are shaped by both genetic and epigenetic factors.
- Early life experiences, including social environment and maternal care, play a crucial role in neurodevelopment.
- Understanding how these early factors influence responses to pharmacological challenges is vital for comprehending developmental trajectories.
Purpose of the Study:
- To investigate the impact of distinct socio-sexual rearing conditions on behavioral and neuroendocrine responses to d-amphetamine (AMPH).
- To examine how maternal deprivation interacts with early social environment to modulate AMPH effects across different developmental ages.
- To determine if early social stimulation influences the hypothalamic-pituitary-adrenal (HPA) axis and monoaminergic system reactivity.
Main Methods:
- CD-1 mouse pups of both sexes were raised in unisexual (all-male, all-female) or mixed-sex litters.
- Pups were tested at postnatal days 3, 8, and 18, under conditions of maternal deprivation (24h) or normal maternal care.
- Behavioral responses and corticosterone (CORT) levels were assessed following d-amphetamine administration.
Main Results:
- Maternal deprivation increased basal and stress-induced CORT secretion in unisexually reared pups, particularly at postnatal day 3.
- Neuroendocrine and behavioral responses to AMPH were often dissociated and modulated by sexual segregation, especially with maternal deprivation.
- AMPH effects on behavior and CORT secretion varied by developmental age, sex, rearing condition, and maternal deprivation status, indicating age- and experience-dependent sensitivity.
Conclusions:
- Early life social environment and maternal deprivation significantly alter neuroendocrine and behavioral responses to amphetamine.
- Maternal deprivation appears to sensitize the monoaminergic system to amphetamine challenges.
- These findings suggest that early social experiences can induce lasting, subtle shifts in central monoaminergic system function, contributing to individual differences.
Abstract:
Individual differences arise from both genetic and epigenetic factors. The aim of this study was to test whether pups raised in distinct socio-sexual conditions would show different behavioural and neuroendocrine responses to d-amphetamine (AMPH) administration upon placement in a novel environment. This issue was addressed by testing infant CD-1 mouse pups of both sexes at three different developmental ages [3, 8, or 18 postnatal (PND) days]. These pups were raised from birth in all-male, all-female, or mixed-sex litters. AMPH effects were assessed as a function of the hypothalamic-pituitary-adrenal (HPA) axis activational state using litters that were either maternally deprived for 24 h (DEP) or normally kept with the dam (NDEP). A concomitant maternal behaviour score carried out on selected postpartum days showed that mothers taking care of all-male litters were more often involved in Active nursing than those rearing the mixed-sex ones, whereas the latter were found more often Laying still out of the nest. Basal and stress-induced corticosterone (CORT) secretion was increased in unisexually reared pups following maternal deprivation, an effect limited to PND 3. In general, neuroendocrine and behavioural responses to AMPH were found to be dissociated and were affected by sexual segregation only in conjunction with maternal deprivation. On PND 3, AMPH injection (1 or 3 mg/kg, i.p.) decreased CORT secretion in deprived unisexually reared subjects without affecting their behaviour. As a whole, behavioural changes due to unisexual rearing were limited to female subjects. On PND 8, unisexually reared females showed, upon maternal deprivation, a generalized shift to the left in the dose-response curve to AMPH for Crossing behaviour, while on PND 18 AMPH-induced stereotypies were considerably reduced in sexually segregated females, especially following maternal deprivation. Thus, maternal deprivation appeared to "sensitize" the monoaminergic system to an AMPH challenge. The individual behavioural and neuroendocrine profiles shown in response to a stressful challenge suggest that changes in social stimulation early during development might produce subtle shifts in the function of selected central monoaminergic systems.