The effects of early rearing environment on the development of GABA(A) andcentral benzodiazepine receptor levels and novelty-induced fearfulness in the rat

We compared the effects of handling or maternal separation from the day fol lowing 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 expl oration 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 dis played: (1) reduced GABA(A) receptor levels in the locus coeruleus (LC) and the n. tractus solitarius (NTS); (2) reduced CBZ receptor sites in the cen tral and lateral n. of the amygdala, the frontal cortex, and in the LC and NTS; and (3) reduced levels of the mRNA for the gamma 2 subunit of the GABA (A) receptor complex, which confers high affinity BZ binding, in the amygda loid nucleic as well as the he LC and NTS. Both the amygdala and the ascend ing nonadrenergic systems have been considered as critical sites for the an xiolytic effects of benzodiazepines. These data suggest that early life eve nts influence the development of the GABA(A) receptor system, thus altering the expression of fearfulness in adulthood. [Neuropsychopharmacology 22:22 9-229, 2000] (C) 2000 American College of Neuropsychopharmacology. Publishe d by Elsevier Science Inc.