Sexually dimorphic changes in the exploratory and... : NeuroReport (original) (raw)

BEHAVIOUR

Sexually dimorphic changes in the exploratory and habituation profiles of heterozygous neuregulin-1 knockout mice

O'Tuathaigh, Colm M.a; O'Sullivan, Gerard J.a; Kinsella, Anthonya; Harvey, Richard P.c; Tighe, Ornab; Croke, David T.b; Waddington, John L.a

Departments of aClinical Pharmacology

bBiochemistry, Royal College of Surgeons in Ireland, Dublin, Ireland and

cVictor Chang Cardiac Institute, University of New South Wales, Sydney, Australia

Correspondence to Colm M. O'Tuathaigh, PhD, Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St Stephen's Green, Dublin 2, Ireland

E-mail: [email protected]

Sponsorship: This study was supported by the Science Foundation Ireland.

Received 20 October 2005; accepted 27 October 2005

Requests for reprints to John L. Waddington, DSc, Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St Stephen's Green, Dublin 2, Ireland

E-mail: [email protected]

Abstract

The neuregulin-1 gene is widely expressed in the central nervous system and is associated with increased risk for schizophrenia. Using an ethologically based approach, the phenotype of neuregulin-1 heterozygous knockout mice was examined by revealing the individual elements of behaviour in the murine repertoire over the prolonged course of interaction with the environment. During initial exploration, neuregulin-1 mutants displayed a phenotype characterized by increases in locomotion and rearing free, with sex-specific alterations in sifting and grooming. Over subsequent habituation, certain initial effects endured while new phenotypic effects emerged, some of which were again sex-specific. These studies elaborate a pleiotropic role of neuregulin-1 in development, plasticity and function, including sexual dimorphism, by defining the elemental, temporal and sex-specific characteristics of the neuregulin-1 mutant ethogram.