Three human and mouse genes encoding adrenoceptor subtypes have been cloned, but the non-availability of subtype-selective pharmacological probes has preculded the characterization of the functional significance of this adrenoceptor heterogeneity. In this study, mice with genetically altered adrenoceptor 2C expression performed differentially from their similarly treated wild-type controls in the forced swimming test, that is a widely used test in the development of antidepressant drugs. In addition, the susceptibility to stress-induced elevations in plasma corticosterone levels was associated with the adrenoceptor mutations. The altered adrenoceptor expression was also found to modify the brain dopamine and serotonin content and neuronal activity marker genes in distinct brain regions. It is suggested that the adrenoceptor 2c is a potential target for yet-to-be-stress-related illnesses, such as depression. The study emphasizes the importance of single-gene mutations in responses to environmental strssors, which may contribute to the manifestation of various neuropsychiatric disorders.
Full reference: J Sallinen, A Haapalinna, E MacDonald, T Viitamaa, J Lähdesmäki, E Rybnikova, M Pelto-Huikko, BK Kobilka, M Scheinin. Genetic alteration of the 2-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels. Mol Psychiatry 1999;4:443-452.
Researchers from the Orion Corporation, Turku, Finland, contributed to the study.
For further information on this work, please contact Dr. Jukka Sallinen Orion Corporation, Orion, Pharma, PO Box 425, FIN-20101 Turku, Finland; Tel: 358-2-272760; FAX: 358-2-2727510; E-mail: jukka.sallinen@orion.fi
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