Dopamine-beta-hydroxylase inhibitors, feeding and locomotor activity: reinstatement of feeding following central norepinephrine.

The effects of two dopamine-beta-hydroxylase (DBH) inhibitors, FLA-63 and fusaric acid (FA) on feeding behaviour and locomotor activity were examined. In Experiment 1 activity was measured over 7 hr in 48 rats treated with FLA-63 (0, 1.25, 2.50, 5.00 mg/kg) or FA (0, 20.0, 40.0, 80.0 mg/kg). While FA produced no significant effect on activity, FLA-63 produced an increase at the highest doses. In Experiment 2 the same doses of the two DBH inhibitors were administered to 48 rats and food intake over 7 hr was measured; both FA and FLA-63 produced decreases in food intake. In a third experiment, rats were stereotaxically implanted with microinjection guide cannulae extending to the ventromedial hypothalamus and, following peripheral treatment with either 5.0 mg/kg FLA-63, 40 mg/kg FA, or their respective vehicles were injected centrally with morphine (5.3 nmoles in 0.5 microliter), norepinephrine (NE; 60 nmoles in 0.5 microliter for the FLA-63 pre-treated group and 30 nmoles in 0.5 microliter for the FA pre-treated group) or saline. Central NE was found to reinstate feeding only in the hr following injection in both groups, while morphine reinstated feeding only in the FA group and only in the third hr following injection. Results support the involvement of hypothalamic NE in feeding.