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Unformatted text preview: Abstract Depression is a growing pandemic in developed societies. The use of inbred mouse strains in pre-clinical psychiatric research has proven to be a valuable resource. Firstly, they provide the background for genetic manipulations that aid in the discovery of molecular pathways that may be involved in major depression. Further, inbred mouse strains are also being used in the determination of genetic and envi- ronmental influences that may pre-dispose or trigger depression-related behavior. This review aims to highlight the utility of inbred mouse strains in depres- sion research, while providing an overview of the cur- rent state of research into behavioral differences between strains in paradigms commonly used in the field. Neurochemical differences that may underlie strain differences are examined, and some caveats and cautions associated with the use of inbred strains are highlighted. Keywords Mouse strains Æ Depression Æ Animal models Æ Antidepressants Introduction ‘‘Strain every nerve to gain your point.’’ Marcus Tullius Cicero (106-43 BC) Depression is one of the most incapacitating and pro- liferating disorders in developed nations (Kessler et al. 1994 ). The World Health Organization predict that unipolar depression will be the second most common cause of debilitating disease by 2020, with an estimated cost in the US of about US$80 billion per year. The most widely used antidepressants in clinical use today are based on the original serendipitously discovered tricyclic antidepressants (TCAs) and monoamine oxi- dase inhibitors (MAOIs), and either block monoamine reuptake or degradation (Frazer 1997b ; Slattery et al. 2004 ). Although these pharmacotherapies are reason- ably efficacious (Frazer 1997b ), against the background of increasing medical need, modern antidepressants therapies are still far from ideal, with a slow onset of action for all antidepressants and relatively high pro- portion of non-responders (about 25–35%). Addition- ally, although side effect profiles have been improved with the advent of selective reuptake inhibitors, it is clear that improvements are still needed (Frazer 1997a ). It is becoming very evident that two of the major contributing factors to the onset of major depression include life stress and genetic pre-disposition (see Charney and Manji 2004 ). Genetic factors have been estimated to account for 40–70% of the risk for developing major depression (Malhi et al. 2000 ; Lesch 2004 ). It is also clear that depressive disorders can re- sult from interactions between a genetic pre-disposi- tion and environmental stimuli (Caspi et al. 2003 ; Edited by Andrew Holmes L. H. Jacobson Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland J. F. Cryan ( & ) Department of Pharmacology and Therapeutics, School of Pharmacy, University College Cork, Cork City, Ireland e-mail: [email protected] Behav Genet (2007) 37:171–213 DOI 10.1007/s10519-006-9106-3 123 REVIEW PAPER...
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This note was uploaded on 10/16/2011 for the course PSYCH 101 taught by Professor Brown,b during the Spring '08 term at BYU.
- Spring '08
- The Land