1. ¹Department of Neurobiology and Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA
2. ²Department of Pharmacology and Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA

Correspondence: Dr P Levitt, Department of Pharmacology, Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Box 40 Peabody, 230 Appleton Place, Nashville, TN 37203, USA. Tel: +1 615 322 8242; Fax: +1 615 322 5910; E-mail: Pat.Levitt@vanderbilt.edu; Dr K Koshibu, Brain Research Institute, University of Zürich/ETH, Bau 55 H38, Winterthuerstrasse 190, CH-8057, Zürich, Switzerland. Tel: +41 01 635 3349; Fax: +41 01 635 3303; E-mail: koshibu@hifo.unizh.ch

Received 14 November 2006; Revised 26 February 2007; Accepted 27 March 2007; Published online 2 May 2007.

Abstract

The maturation of many neural functions occurs during puberty. An abnormal development of these processes, in the context of genetic vulnerability, may result in sex- and age-dependent penetrance of neuropsychiatric disorders. Reduced transforming growth factors- (TGF-) expression in Waved-1 (Wa-1) mice impairs the stress response and fear memory in adult males, but are absent or far less prominent in adult females and in pubertal males. Gonadectomy around the onset of puberty, when the mutant anatomical and behavioral phenotypes are undetectable, results in significant gene environment effects. Adult control males show reduced physiological stress response as a result of gonadectomy, but not adult Wa-1 males. In females, pubertal gonadectomy elevates specific anxiety parameters only in adult control mice. There also are general sex-specific effects of pubertal gonadectomy on adult stress and fear memory. Surgical stress alone also induces sex- and genotype-dependent effects, albeit in different behavioral parameters than those affected by gonadectomy. We conclude that normal development of stress and memory processes is reliant on the levels of stress and gonadal factors during puberty, the effects of which are modulated by genetic factors and sex.