Abstract
The monoamine and opioid systems control emotional and addictive behaviors. Transgenic mice lacking monoamine transporter gene or opioid receptor gene have been produced by gene targeting. Behavioral analysis of these mutant animals has highlighted distinct roles of monoamine transporter and opioid receptor and revealed their important roles in emotional behaviors. The examinations of responses to addictive drugs have clarified involvement of monoamine transporter and opioid receptor as molecular targets for emotional behavior. The conditioned place preference (CPP) paradigm and intravenous self-administration are popular behavioral paradigms for reward system. Many of the findings from these studies have been quite surprising; for instance, cocaine retains its rewarding effect in dopamine transporter (DAT) knockout mice indicating a polygenic basis of psychostimulant reward. Such studies are also some of the first attempts to examine gene-gene interactions behaviorally in a specific manner. We have examined extracellular dopamine and serotonin release using in vivo microdialysis in the strains of knockout mice with normal or enhanced psychostimulant reward. Those data have demonstrated the critical roles of monoamine transporter and opioid receptor, and confirmed their involvement in several emotional responses. Ongoing studies therefore help in understanding the molecular basis of emotional behaviors and will contribute to the development of novel therapeutics for mental disorders including drug abuse. [Jpn J Physiol 54 Suppl:S27 (2004)]
