Abstract
We compared the effects of handling or maternal separation from the day following birth until postnatal day 14 on behavioral responses to novelty and on GABAA and central benzodiazepine (CBZ) receptor levels in the rat. As adults, handled animals showed reduced startle responsivity, increased exploration in a novel open field, and decreased novelty-induced suppression of feeding relative to the handled (H) and/or maternal separation (MS) groups. As compared with handled animals, both nonhandled (NH) and MS animals displayed: (1) reduced GABAA receptor levels in the locus coeruleus (LC) and the n. tractus solitarius (NTS); (2) reduced CBZ receptor sites in the central and lateral n. of the amygdala, the frontal cortex, and in the LC and NTS; and (3) reduced levels of the mRNA for the γ2 subunit of the GABAA receptor complex, which confers high affinity BZ binding, in the amygdaloid nuclei as well as in the LC and NTS. Both the amygdala and the ascending noradrenergic systems have been considered as critical sites for the anxiolytic effects of benzodiazepines. These data suggest that early life events influence the development of the GABAA receptor system, thus altering the expression of fearfulness in adulthood.
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Acknowledgements
This research was supported by NIMH Grant MH50113 to PMP and MJM and by a grant from the Medical Research Council of Canada to MJM. MJM is supported by a MRCC Senior Scientist career award from the Medical Research Council of Canada. CC is supported by a graduate fellowship from the Fonds de la Recherche en Santé du Québec (FRSQ).
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Caldji, C., Francis, D., Sharma, S. et al. The Effects of Early Rearing Environment on the Development of GABAA and Central Benzodiazepine Receptor Levels and Novelty-Induced Fearfulness in the Rat. Neuropsychopharmacol 22, 219–229 (2000). https://doi.org/10.1016/S0893-133X(99)00110-4
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DOI: https://doi.org/10.1016/S0893-133X(99)00110-4
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