Feeding behavior in dopamine-deficient mice

Mice that cannot make dopamine (DA), a condition caused by the selective in activation of tyrosine hydroxylase in dopaminergic neurons, are born normal but gradually become hypoactive and hypophagic, and die at 3 weeks of age. We characterized the feeding and locomotor responses of these DA-deficient (DA-/-) mice to 3,4-dihyroxy-L-phenylalanine (L-DOPA) to investigate the r elationship between brain DA revels and these complex behaviors. Daily admi nistration of L-DOPA to DA-/- mice stimulated locomotor activity that laste d 6 to 9 hr; during that time the mice consumed most of their daily food an d water. The minimal dose of L-DOPA that was sufficient to elicit normal fe eding behavior in the DA-/- mice also restored their striatal DA to 9.1% of that in the wild-type (WT) mice at 3 hr; then DA content declined to <1% o f WT levels by 24 hr. This dose of L-DOPA induced locomotor activity that e xceeded that of treated WT mice by 5- to 7-fold, suggesting that DA-/- mice are supersensitive to DA. Unexpectedly, DA-/- mice manifested a second wav e of activity 24 to 48 hr after L-DOPA treatment that was equivalent in mag nitude to that of WT mice and independent of DA receptor activation. The DA -/- mice approached, sniffed, and chewed food during this second period of activity, but they ate <10% of that required for sustenance. Therefore, DA- /- mice can execute behaviors necessary to seek and ingest food, but they d o not eat enough to survive.