The effect of early maternal separation on brain derived neurotrophic factor and monoamine levels in adult heterozygous reeler mice.

OBJECTIVE AND METHODS: The reeler heterozygous (HZ) mice have provided a model for studying the relationship between reelin (a protein of extracellular matrix) haploinsufficiency and the emergence of neuropsychiatric diseases. In a neurodevelopmental framework, the enduring consequences of early maternal separation (5 h/day during the first postnatal week, or handling controls, H) were studied in reeler HZ and wild type (WT) mice at adulthood. The modulatory effects of a chronic treatment with the atypical antipsychotic olanzapine (OLZ, 1.5 mg/kg for 40 days) were also investigated.

RESULTS: Early maternal separation had long-term effects on brain plasticity, with a reduction of brain- and glial- derived neurotrophic factor (BDNF and GDNF) in several brain areas of mice, but such a consequence was less marked in the HZ genotype. On the other hand, treatment with OLZ did not affect at all the GDNF but led to an increase of BDNF levels in maternally separated (SEP) mice, an effect which was far more marked in the HZ genotype. Brain levels of serotonin (5-HT) were markedly increased, striatal dopamine (DA) was increased, whereas metabolites and turnover were decreased, in SEP mice of both genotypes. The spontaneous home-cage activity was generally lower in HZ than WT mice, and OLZ treatment contrasted this hypoactivity profile. Maternal separation also decreased the interest toward an unknown mouse proposed as a social stimulus, but only in WT mice.

CONCLUSION: We investigated the interplay between genetic vulnerability (reelin haploinsufficiency), the outcome of early stressful experiences, and the efficacy of the antipsychotic drug therapy. The reeler HZ genotype exhibited a slightly lower sensitivity to the environmental insult as well as an enhanced response to the atypical antipsychotic treatment.