Dopamine production in the caudate putamen restores feeding in dopamine-deficient mice

Dopamine-deficient (DD) mice cannot synthesize dopamine (DA) in dopaminergi c neurons due to selective inactivation of the tyrosine hydroxylase gene in those neurons. These mice become hypoactive and hypophagic and die of star vation by 4 weeks of age. We used gene therapy to ascertain where DA replac ement in the brain restores feeding and other behaviors in DD mice. Restora tion of DA production within the caudate putamen restores feeding on regula r chow and nest-building behavior, whereas restoration of DA production in the nucleus accumbens restores exploratory behavior. Replacement of DA to e ither region restores preference for sucrose or a palatable diet without fu lly rescuing coordination or initiation of movement. These data suggest tha t a fundamental difference exists between feeding for sustenance and the ab ility to prefer rewarding substances.