5‐Methoxypsoralen enhances plasma melatonin concentrations in the male rat: Non‐noradrenergic‐mediated stimulation and lack of effect in pinealectomized animals

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Abstract
Previous studies have shown that 8‐methoxypsoralen (8‐MOP) is able to enhance melatonin secretion from rat pineal glands. The effect of another psoralen, 5‐methoxypsoralen (5‐MOP) on plasma melatonin concentrations alone or in combination with isoproterenol (Iso, 10 mg/kg BW, i.p.) or propranolol (Prop, 20 mg/kg BW, s.c.) was studied in the rat. An increase in plasma melatonin concentrations was observed 1 h after psoralen administration and lasted 8 h. The stimulatory effect of 5‐MOP on circulating melatonin concentrations was dose dependent above 5‐mg/kg, BW. 5‐MOP also potentiated the Iso‐induced rise in plasma melatonin levels. Furthermore, Prop did not block the effect of 5‐MOP, indicating that the psoralen acts independently of the noradrenergic system controlling pineal melatonin synthesis. No increase in plasma melatonin levels was observed in pinealectomized (Px) animals after injection of 5‐MOP (20 mg/kg BW) or 8‐MOP (20 mg/kg BW). This demonstrates that the rise in plasma melatonin concentrations observed after treatment requires the presence of the pineal gland, and that neither 5‐MOP nor 8‐MOP stimulates melatonin release from other structures such as the retina or Harderian gland.