Effects of levodopa and dopamine of plasma glucose concentration in mice

In nialamide-treated, fasted mice levodopa produced a dose-dependent hypoglycaemic response. The response was also seen in pargyline-treated mice but not in animals which were not treated with a monoamine oxidase inhibitor. Dopamine did not affect plasma glucose under these conditons. In doses which were ineffective when injected i.v., both levodopa and dopamine produced hypoglycemia when injected intracerebroventriculary (i.c.v.). The hypoglycaemic response to levodopa was prevented by the dopamine antagonists, haloperidol and pimozide. The possible involvement of 5HT in the hypoglycaemic response to levodopa was suggested by the blockade of the response by cyproheptadine and methysergide together with the observations that hypoglycaemia is produced by 5HTP and by i.c.v. 5HT. p-Chlorophenylalanine (PCPA) also reduced the response to levodopa but the usefulness of PCPA as an inhibitor of 5HT synthesis in these experiments in doubtful since it also inhibited the hypoglycaemic effects of 5HTP and i.c.v. 5HT. Hypoglycaemia produced by levodopa did not appear to involve stimulation of insulin secretion since plasma IRI levels were not increased by levodopa and the hypoglycaemia was accompanied by a elevation of plasma FFA and no significant change in the liver glycogen content. It is suggested that the hypoglycaemic effect of levodopa is mediated through dopamine acting in the brain, although the involvement of 5HT in the response and the mechanisms involved remain to be determined.