Genetic approaches to studying norepinephrine function: Knockout of the mouse norepinephrine transporter gene

Norepinephrine is an important chemical messenger in the nervous system. It regulates affective states, learning and memory, endocrine and autonomic f unctions. It has been implicated in depression, aggression, and addiction, as well as cardiac and thermal dysregulation. The norepinephrine transporte r functions by uptaking norepinephrine back into the cell for cyclic use, a nd is a direct target of a number of antidepressants and psychostimulants. Functional deletion (knockout) of monamine transporters results in increase s in extracellular levels of neurotransmitters, thereby prolonging their ac tions. For the norepinephrine transporter knockout mice, this altered state of the norepinephrine system should simulate the therapeutic effects of no repinephrine selective antidepressants and some of the effects of psychosti mulants. Careful use of such an animal model can hopefully provide valuable insight into the multiple roles norepinephrine plays in normal and patholo gical physiology. (C) 1999 Society of Biological Psychiatry.