The Effects of Early Rearing Environment on the Development of GABAA and Central Benzodiazepine Receptor Levels and Novelty-Induced Fearfulness in the Rat

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 GABA_A 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 GABA_A 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 GABA_A 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 GABA_A receptor system, thus altering the expression of fearfulness in adulthood.

[Neuropsychopharmacology 22:219–229, 2000] © 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.