Effect of chlorpromazine, 5-hydroxytryptophan, and benserazide on plasma melatonin in the mudpuppy, Nectvrus maculosus

Abstract

1. Melatonin (MEL) was measured by radioimmunoassay in adult Necturus maculosus treated with a melatonin precursor, 5-hydroxy- l-tryptophan (5HTP), a melatonin antimetabolite, chlorpromazine (CPZ), or an l-aromatic amino acid decarboxylase inhibitor, benserazide (BNS, Ro4-4062). MEL concentrations during photophase were significantly higher in animals receiving 5HTP (10, 20, 40 mg kg −1 ) than in saline-injected controls after 4 hr. 2. In animals receiving CPZ (2 or 20 mg kg −1) over a 3-day treatment schedule and sampled from 4 to 6 hr after injection, MEL was significantly higher than in controls whether sampled during midphotophase or midscotophase. Mean MEL in scotophase-sampled animals receiving 20 mg kg −1 was four times the concentration in midophotophase controls. 3. An ip dose of benserazide (50 or 80 mg kg −1) 3 hr after onset of photophase significantly reduced MEL compared with controls 3 hr after injection. The melatonin concentrations in animals receiving 80 mg kg −1 were only 4% of that in controls after 6 hr; MEL had recovered to 75% of control concentrations after 12 hr. 4. These experiments indicate that in Necturus: (1) MEL agonists can augment pathway enzyme activity during photophase; (2) a peripheral l-aromatic amino acid decarboxylase inhibitor operates under the same mechanism as in higher vertebrates; (3) chlorpromazine inhibition of MEL metabolism is effective day or night in increasing circulating MEL.