Short communication Sex-specific development of cortical monoamine levels in mouse Shelley Connell a , Collins Karikari b , Christine F. Hohmann c, * a Doctoral Studies Program in Math and Science Education, Morgan State University, 1700 E. Cold Spring Ln., Baltimore, MD 21251, USA b National Institute of Allergy and Infectious Diseases, Laboratory of Parasitic Diseases/NIH, 9000 Rockville Pike, Bldg. 4 Rm. B2-39, Bethesda, MD 20892-1886, USA c Department of Biology, Morgan State University, 1700 E. Cold Spring Ln., Baltimore, MD 21251, USA Accepted 16 March 2004 Available online 4 June 2004 Abstract Several mental health disorders exhibit sex differences in monoamine levels associated with dimorphic cortical ontogeny. Studies in rodents support the notion that monoamines can profoundly modulate morphogenesis. Here, we show significant sex and hemisphere differences in BALB/cByJ mice on postnatal day 3 for dopamine (DA) and serotonin (5-TH), supporting the notion that sex differences in early monoaminergic ontogeny may result in dimorphic cortical development. Such sex differences may also influence differential behavioral and/or clinical outcomes. D 2004 Elsevier B.V. All rights reserved. Theme: Neural basis of behavior Topic: Monoamines Keywords: Mouse; Ontogeny; High performance liquid chromatography; Dimorphism; Mental health Mental health disorders such as schizophrenia, mood disorders and autism have been known to affect males and females differentially [10,14,16,25]. A shared feature in their pathobiology is the involvement of afferent monoam- inergic (MA) projections. Additionally, most have shown indications of early developmental disruptions in MA in- nervation as well as altered cortical morphogenesis and plasticity [6,10,18,22,29,30,37]. Animal models strongly suggest that morphological and behavioral pathologies can result from developmentally al- tered brainstem MA innervation of cortical targets [7,23]. Many studies have demonstrated that early postnatal alter- ations in catecholaminergic (CA) and serotonergic (5-HT) innervation impact neuronal differentiation and plasticity by interfering with the normal time course of process outgrowth and synaptic formation and pruning [4,6,7,15,24]. Moreover, recent studies from our laboratory have shown that focal neonatal depletions of MA projections to neocortex will lead to profound sex dimorphisms in ontogeny [1,20]. Sex differences in MA, particularly DA projections to many parts of the nervous system, including cerebral cortex, have been indicated in humans and rodents [11,14,28]. However, the current literature disagrees on when and how such sex differences might come into existence [9,27,31]. Several investigators studying the early development of MA nuclei in the brainstem and dienceph- alon were unable to detect statistically significant sex differences [3,38]. On the other hand, Lieb et al. [26] and Reisert and Pilgrim [31] were able to measure, prenatally, an altered distribution and a 30% increase in the male number of brainstem neurons immunoreactive for tyrosine hydroxylase, an enzyme active in the synthesis pathways of both NE and DA. Furthermore, developmental manipula- tions of sex steroids or stressful experiences have been able to induce sex differences in cortical monoamine markers [5,34,35]. High performance liquid chromatography (HPLC) stud- ies of monoamine levels in forebrain and diencephalon have largely failed to show early developmental sex differences. However, past studies rarely have explored cortical mono- amine levels within the first few days after birth; none have separately assayed levels in male and female cerebral cortex [12,19]. 0165-3806/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.devbrainres.2004.03.008 * Corresponding author. Tel.: +1-443-885-4002; fax: +1-443-885- 8582. E-mail address: Chohmann@morgan.edu (C.F. Hohmann). www.elsevier.com/locate/devbrainres Developmental Brain Research 151 (2004) 187 – 191