Neonatal handling and the maternal odor preference in rat pups: involvement of monoamines and cyclic AMP response element-binding protein pathway in the olfactory bulb
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Updated: Jun 26, 2026

A Lateralized Odor Learning Model in Neonatal Rats for Dissecting Neural Circuitry Underpinning Memory Formation
Published on: August 18, 2014
C Raineki1, M A De Souza, R E Szawka
1Laboratório de Neuroendocrinologia do Comportamento, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, 90050-170, RS, Brazil.
Insights
Neonatal handling alters maternal odor preference in female pups but not males. Early life stress impacts olfactory bulb neurochemistry, revealing sex differences in rat pups.
Area of Science:
- Neuroscience
- Developmental Psychology
- Animal Behavior
Background:
- Early-life environmental factors, like handling, can cause lasting changes in behavior and neuroendocrine systems.
- The specific pup-level changes linking early handling to adult effects are not well understood.
- Investigating neonatal responses is crucial for understanding long-term developmental impacts.
Purpose of the Study:
- To examine the effects of neonatal handling on maternal odor preference and olfactory bulb (OB) neurochemistry in 7-day-old rat pups.
- To identify sex-specific differences in behavioral and biochemical responses to neonatal handling.
- To explore the relationship between OB neurochemical changes and maternal odor preference.
Main Methods:
- Neonatal rat pups (male and female) were subjected to repeated handling (RH), single handling (SH), or no handling (NH).
- Maternal odor preference was assessed behaviorally.
- Biochemical analyses included cyclic AMP response element-binding protein (CREB) phosphorylation, noradrenaline (NA), and serotonin (5-HT) levels in the OB.
- Data were analyzed to compare behavioral and biochemical parameters across handling groups and sexes.
Main Results:
- Repeated handling (RH) abolished maternal odor preference in female pups, unlike in males.
- RH decreased noradrenaline (NA) activity in the OB of both sexes.
- Serotonin (5-HT) activity in the OB increased only in RH male pups.
- CREB phosphorylation in the OB was not affected by RH in either sex.
Conclusions:
- Neonatal handling significantly impacts maternal odor preference and OB neurochemistry in rat pups, with notable sex differences emerging by 7 days of age.
- The maintenance of maternal odor preference in handled males may be linked to increased OB serotonin levels despite reduced noradrenaline.
- These findings highlight that early environmental interventions can shape crucial behavioral and biochemical mechanisms even in the neonatal period.
Abstract:
Early-life environmental events, such as the handling procedure, can induce long-lasting alterations upon several behavioral and neuroendocrine systems. However, the changes within the pups that could be causally related to the effects in adulthood are still poorly understood. In the present study, we analyzed the effects of neonatal handling on behavioral (maternal odor preference) and biochemical (cyclic AMP response element-binding protein (CREB) phosphorylation, noradrenaline (NA), and serotonin (5-HT) levels in the olfactory bulb (OB)) parameters in 7-day-old male and female rat pups. Repeated handling (RH) abolished preference for the maternal odor in female pups compared with nonhandled (NH) and the single-handled (SH) ones, while in RH males the preference was not different than NH and SH groups. In both male and female pups, RH decreased NA activity in the OB, but 5-HT activity increased only in males. Since preference for the maternal odor involves the synergic action of NA and 5-HT in the OB, the maintenance of the behavior in RH males could be related to the increased 5-HT activity, in spite of reduction in the NA activity in the OB. RH did not alter CREB phosphorylation in the OB of both male and females compared with NH pups. The repeated handling procedure can affect the behavior of rat pups in response to the maternal odor and biochemical parameters related to the olfactory learning mechanism. Sex differences were already detected in 7-day-old pups. Although the responsiveness of the hypothalamic-pituitary-adrenal axis to stressors is reduced in the neonatal period, environmental interventions may impact behavioral and biochemical mechanisms relevant to the animal at that early age.
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